Descriptive evaluation of a camera-based dairy cattle lameness detection technology.

Lameness in dairy cattle is a clinical sign of impaired locomotion, mainly caused by painful foot lesions, compromising the US dairy industry's economic, environmental, and social sustainability goals. Combining technology and on farm data may be a more precise and less labor-intensive lameness detection tool, particularly for early detection. The objective of this observational study was to describe the association between average weekly autonomous camera-based (AUTO) locomotion scores and hoof trimming (HT) data. The AUTO data were collected from 3 farms from April 2022 to March 2023. Historical farm HT data were collected from March 2016 to March 2023 and used to determine cow lesion history and date of HT event. The HT events were categorized as a regular HT (TRIM; n = 2290) or a HT with a lesion recorded (LESION; n = 670). Events with LESION were sub-categorized based on lesion category: digital dermatitis (DD; n = 276), sole ulcer (SU; n = 79), white line disease (WLD; n = 141), and other (n = 174). The data also contained the leg of the LESION, classified as front left (FL; n = 54), front right (FR; n = 146), rear left (RL; n = 281), or rear right (RR; n = 183) leg with 6 events missing the leg. Cows' HT histories were classified as follows: cows with no previous recorded instance of any lesion were classified as TRIM0 (n = 1554). The first instance of any hoof lesion was classified as LESION1 (n = 238). This classification was retained until a subsequent TRIM occurred - recorded as TRIM1 (n = 632). The next unique instance of any lesion following a TRIM1 was classified as LESION2 (n = 86). Any LESION events occurring after LESION1 or LESION2 without a subsequent TRIM were considered a hoof lesion recurrence and classified as LESIONRE1 (n = 164) and LESIONRE2 (n = 22), respectively. TRIM events after LESION2 or LESION2RE (n = 104) or LESION events after LESIONRE1 or LESIONRE2 were classified as LESION_OTHER (n = 160). The AUTO scores from -28 to -1 days prior to the HT event were summarized into weekly scores and included if cows had at least 1 observation per week in the 4 weeks before the event. For all weeks, LESION cows had a higher median AUTO score than TRIM cows. Cows with TRIM0 had the lowest and most consistent median weekly score compared to LESION and other TRIM classifications. Before HT cows with TRIM0 and TRIM1, both had median score increases of 1 across the 4 weeks, while the LESION categories had an increase of 4 to 8. Scores increased with each subsequent LESION event compared to the previous LESION event. Cows with SU lesions had the highest median score across the 4 weeks, WLD had the largest score increase, and DD had the lowest median score and score increase. When grouping a LESION event by leg the hoof lesion was found on, the AUTO scores for four groups displayed comparable median values. Due to the difference between TRIM and LESION events, this technology shows potential for the early detection of hoof lesions.

Randomized clinical trial evaluating the effects of administering acidogenic boluses at dry-off on udder health, milk yield, and herd removal.

Acidogenic boluses can mitigate potential negative effects of high milk yield at dry-off on udder health. This randomized controlled trial aimed to investigate the effect of administering acidogenic boluses at dry-off on dry period intramammary infection (IMI) dynamics and on milk production parameters, somatic cell count linear score (LSCC), clinical mastitis (CM), and herd removal in the next lactation. A total of 901 cows from 3 dairy farms were randomly allocated to a control (CON, n = 458; no administration of acidogenic boluses at dry-off) or treatment group (TRT, n = 443; administration of 2 acidogenic boluses at dry-off). Quarter milk samples were collected at dry-off and after calving and submitted for bacteriological milk culture. The effects of treatment on the presence of quarter-level postpartum IMI, cure of existing IMI, and acquisition of new IMI, and on the prevalence of cow-level high LSCC (LSCC ≥4) in the first 30 days in milk (DIM) were analyzed using mixed effects logistic regression. Mixed linear regression was used to analyze cow-level milk production parameters (i.e., milk yield, fat corrected milk, fat and protein yield, and LSCC) in the first 90 DIM and until 300 DIM. For CM and herd removal, Cox proportional hazard regression models were used. In addition to treatment group, lactation group at dry-off, presence of high LSCC in the last test-day, average milk yield in the week before dry-off, presence of CM in the lactation of enrollment, and biologically relevant interactions were offered in all models. There was no evidence of a difference in IMI dynamics or in milk, fat corrected milk, protein or fat yields in the subsequent lactation between groups. The TRT group had a lower LSCC in the first 2 mo postpartum compared with the CON group (2.58 ± 0.3 vs. 2.92 ± 0.3 and 2.42 ± 0.3 vs. 2.81 ± 0.3, for first and second month postpartum). The prevalence of high LSCC in the first 30 DIM was 9.1% lower in the TRT compared with the CON group (16.3% vs. 25.5%; risk difference: -9.2; 95% confidence interval [CI]: -15.8, -2.5). Cows in the TRT group exhibited reduced hazards of CM in the subsequent lactation compared with cows in the CON group (hazard ratio: 0.75; 95% CI: 0.63, 0.89) as well as a reduced hazard of herd removal (hazard ratio: 0.82, 95% CI: 0.77, 0.88). The administration of acidogenic boluses as a component of dry-off management is a promising approach to maintain good udder health and reduce the hazard of CM and herd removal during the subsequent lactation.

An iterative approach to the development of a sole ulcer induction model in Holstein cows.

Our objective was to develop a sole ulcer (SU) induction model that can be used to investigate new and more efficacious methods for the treatment and prevention of SU. Three iterations [phase (P)1, P2, and P3] of an SU induction model designed to mimic mechanical and presumed metabolic pathways for SU development were conducted. The results from P1 and P2 identified alterations for the subsequent phase. Each phase used cows with similar calving dates that were randomly assigned (n = 4) to treatments. Control cows (P1CON, P3CON) did not undergo any challenges to induce SU development. Treatment cows were challenged with a hoof block (B) applied to the right hind lateral hoof. Other treatments included restricted lying time (L), restricted feed intake (F), or systemic lipopolysaccharide (LPS) administration. Treatment comparisons were P1CON versus P1BL, P2B versus P2BL, and P3CON versus P3BLF and P3BLF+LPS for P1, P2, and P3, respectively. Pregnant nulliparous Holstein cows were used in P1 and P3, and the P1 cohort was used in P2 during mid-lactation [125.9 ± 7.20 d in milk (DIM)]. Challenges were applied during a set challenge period (P1: -14 to 14 DIM, P2: 126-168 DIM, P3: -14 to 28 DIM). The P1BL cows had a hoof block applied and lying time restricted for 5 h/d. The P2B and P2BL cows had a hoof block and P2BL cows also had their lying time restricted for 18 h/d for 2 d/wk. The P3BLF and P3BLF+LPS cows had a hoof block, 6 h/d of lying time restricted 2 d/wk, and had their DMI restricted by 30% for 2 d/wk. At weekly intervals during wk 1 to 3 postpartum, P3BLF+LPS cows received jugular administration of 0.031, 0.062, and 0.125 µg of LPS per kg of body weight, respectively. Primary response measurements included hoof lesion and locomotion scoring, lying time, hoof thermography, and weight distribution per hoof. No SU induction occurred but sole hemorrhages, a precursor to SU, occurred during the postchallenge period of all phases. Temperature of the blocked hoof at the end of the challenge period did not change for P3CON cows but increased by 5.5°C and 6.2°C for P3BLF and P3BLF+LPS, respectively. Notable increases in lameness and lack of weight-bearing on the blocked hind hoof occurred for challenge treatment cows during the challenge period of P2 and P3. These changes did not persist after the hoof blocks were removed, indicating that hoof blocks succeeded in altering cow gait mechanics, but not enough to induce long-term lameness or SU. Lying restriction challenged cows in P2 and P3, indicated by a compensatory increase in lying time on the day following lying restriction compared with that on the day before restriction. In P3, lying time had the greatest depression during restriction and compensation following restriction in P3BLF+LPS cows, with LPS challenges potentially increasing the other challenge's effects. Future iterations of the SU induction model should include hoof block use, evaluate longer and more frequent standing and inclusion of forced walking bouts, and include DMI and LPS metabolic challenges.

Using a target trial approach to evaluate the role of hyperketonemia in sole ulcer and white line hoof lesion development.

This observational cohort study enrolled cows from 7 freestall dairy herds in Minnesota and Wisconsin. The objective was to estimate the causal role of hyperketonemia on new sole ulcer and white line hoof lesions (SUWL). Multiparous cows were enrolled at the time of their precalving hoof trim, at the end of their previous lactation. Enrolled cows were hoof trimmed twice: precalving between 90 to 21 d before calving (n = 2,037), and postcalving between 21 to 150 d after calving (n = 1,408). We trained 7 commercial hoof trimmers, employed by the farms, in lesion identification to standardize lesion recording. Hoof trimmers conducted therapeutic trimming as well as diagnosing and treating lesions. After parturition, cows between 3 and 16 d in milk were tested once weekly for hyperketonemia using a hand-held ketone meter. Farm staff and research personnel conducted the ß-hydroxybutyrate (BHB) testing. Cows were classified as hyperketonemic (HYK+) if they had a blood BHB ≥1.2 mmol/L or hyperketonemia-negative (HYK-) if blood BHB <1.2 mmol/L. At the precalving hoof trim, 15.6% of cows trimmed had a lesion and 1.9% of cows had a SUWL; thus, cows with a SUWL were excluded from further analysis (n = 38). At the postcalving hoof trim, 25.8% of cows trimmed had a hoof lesion, and 3.6% of cows had a SUWL. The most prevalent lesions at the pre- and postcalving hoof trims were digital dermatitis and corkscrew lesions. The incidence of hyperketonemia among cows was 21.1% (421/1,999) and the incidence on farms ranged from 5.7 to 29.1%. After excluding cows due to being hoof trimmed outside our designated window, the multilevel logistic regression model for the odds of SUWL at the postcalving hoof trim included 1,209 cows (HYK+ = 257/1,209; SUWL = 42/1,209). The odds of having SUWL in HYK+ was 0.66 (95% confidence interval: 0.29, 1.49) times the odds of that for HYK- cows. For cows diagnosed with a lesion (digital dermatitis, corkscrew, toe, foot rot, or other lesion) at their precalving hoof trim (n = 199), the odds of having SUWL for HYK+ cows were 0.43 (95% confidence interval: 0.05, 3.92) times the odds of that for HYK- cows. The wide range of compatible causal estimates suggest that hyperketonemia likely has a limited role in the development of SUWL in cows with or without a hoof lesion precalving. Future research should investigate other transition period factors such as inflammation or structural changes to the foot that may have a causative role in the development of SUWL.

Promoting farm advisor engagement and action toward the improvement of dairy cattle lameness.

Lameness represents a significant management challenge in the dairy industry worldwide. In addition to farmers, many advisors are involved in lameness management, including veterinarians, hoof trimmers, and nutritionists. These advisors support farmers through lameness prevention practices, treatments, and advice, but little is known about how advisors view others' roles and the extent to which they work together. This study used qualitative participatory methods to facilitate the formation of lameness advisory groups among 13 advisors (4 veterinarians, 5 hoof trimmers, and 4 nutritionists), with the aims of promoting advisors' engagement with one another and documenting their perceptions of the benefits and challenges of the research activities through semi-structured interviews and thematic analysis. Participants shared predominantly positive views toward the project and voiced appreciation about the quality of discussions and the opportunity to connect and build relationships with other advisors. Participants reported improved communication with others via sharing reports and farm information, as well as increased confidence in reaching out to other advisors. Reported challenges included time constraints and discomfort in leading the lameness advisory group meetings. Difficulties were also found in bringing issues to farmers' attention when they might not align with the farmers' goals or priorities, as well as participants' questioning other advisors' knowledge and intentions. This study describes a promising avenue of facilitating advisor engagement, although more work is needed to determine whether such engagement translates to a reduction of lameness on farms.

Assessment of milk yield and composition, early reproductive performance, and herd removal in multiparous dairy cattle based on the week of diagnosis of hyperketonemia in early lactation.

The purpose of this retrospective cohort study was to evaluate the effects of the timing of hyperketonemia (HYK) diagnosis during early lactation on milk yield and composition, reproductive performance, and herd removal. Plasma ß-hydroxybutyrate (BHB) was measured twice a week during the first 2 wk of lactation in 362 multiparous Holstein cows for the diagnosis of HYK. In each week, cows were diagnosed as HYK positive (HYK+) if the plasma BHB concentrations were ≥1.2 mmol/L in at least one of the tests for the week evaluated. Milk-related outcomes (first 10 monthly milk tests) included milk yield, milk fat and protein content, milk urea nitrogen (MUN), and linear score of somatic cell count. Other performance outcomes of interest included risk of pregnancy within 150 d in milk (DIM) and herd removal (i.e., culling or death) within 300 DIM. Statistical models were built separately for cows diagnosed with HYK during the first week of lactation (wk1) and for cows diagnosed during the second week of lactation (wk2). All models for wk2 were adjusted by HYK diagnosed in wk1, along with other potential confounder variables. The association between HYK in each week and milk-related outcomes was assessed using generalized estimated equation models that accounted for repeated measures. Time to pregnancy and time to herd removal were analyzed using Cox's proportional hazard regression models. Seventy-eight cows (21.5%) tested positive for HYK during wk1, 60 cows (16.6%) in wk2, and 29 cows (8.0%) in both weeks. Hyperketonemia during wk1 was associated with a milk yield reduction of 3.7 kg [95% confidence interval (CI): -6.67 to -0.76] per cow per day throughout the lactation. Meanwhile, we did not observe evidence of an association between HYK diagnosed during wk2 and milk yield. During the first 2 monthly milk tests, cows diagnosed as HYK+ in wk1 had greater fat (0.42%; 95% CI: 0.16 to 0.67) and MUN (0.75 mg/dL; 95% CI: 0.26 to 1.24) content in milk than HYK-negative (HYK-) cows. We did not detect any evidence of an association between HYK diagnosed in wk2 and these outcomes. The HYK+ cows in wk1 had a 30% [hazard ratio (HR) = 0.70; 95% CI: 0.48 to 1.01] lower risk of pregnancy within 150 DIM and 2.48 times (95% CI: 1.63 to 2.89) higher risk of herd removal within 300 DIM than HYK- cows. Conversely, no evidence of association was observed between HYK+ cows in wk2 and risk of pregnancy by 150 DIM (HR = 0.98; 95% CI: 0.64 to 1.51) or removal from the herd within 300 DIM (HR = 0.91; 95% CI: 0.52 to 1.60). Our findings indicate that HYK diagnosed during wk1 of lactation is associated with negative performance in terms of milk yield, reproduction, and herd removal. No evidence of association was found for the same outcomes when HYK was diagnosed in wk2. Our results suggest the need to consider the timing when HYK is diagnosed when investigating its association with performance outcomes.

Dairy farmer, hoof trimmer, and veterinarian perceptions of barriers and roles in lameness management.

Lameness is a leading animal welfare concern in the dairy industry. Multiple stakeholders are involved in lameness management on a dairy farm, including farmers, hoof trimmers, and veterinarians. This study sought to explore perceptions of lameness, perceptions of roles in lameness management, and barriers to improved lameness management in these groups. Fourteen homogeneous focus groups were held in Minnesota, Wisconsin, and New York from April 2017 to March 2020; 5 with farmers (n = 31), 4 with hoof trimmers (n = 32), and 5 with veterinarians (n = 25). The 1-h facilitated discussions were audio-recorded, transcribed verbatim, and common themes identified through thematic analysis. Lameness was perceived by participants as a complex health problem and one in which the connections between pathogenesis, facilities, and management were not always well understood or easy to change. The complexity of the problem encompassed the lack of agreement on a definition of lameness, normalization to its signs, and the interconnectedness of lameness with other health and management issues. These issues appeared to contribute to resignation by participants that lameness was inevitable. Despite shared concerns about lameness among these groups, respondents reported a lack of communication, especially between hoof trimmers and veterinarians. Participants also voiced a desire to work together more productively, with hoof trimmers and veterinarians valuing the ability to deliver a consistent message to farmers. These findings suggest a need for increased efforts to facilitate collaboration between farmers, hoof trimmers, and veterinarians to improve lameness management on dairy farms.

Evaluating the association between early-lactation lying behavior and hoof lesion development in lactating Jersey cows.

Objectives were to evaluate the association between behavior and hoof lesions (HL) in lactating dairy cows. Jersey cows without any visible HL on all 4 legs were enrolled at 20 ± 3 d in milk (DIM), examined for body condition score (BCS), and had an automatic activity monitor (AfiTag II, AfiMilk, Afikim, Israel) attached to their right hind leg. At 120 ± 3 DIM, activity monitors were removed and cows were re-examined for HL and BCS. Cows were classified according to HL status as either healthy or with HL at d 120. Because sole hemorrhage (SH) accounted for over 80% of HL on d 120, SH was reclassified according to the number of feet affected. Daily activity data (daily lying duration, lying bouts, lying bout duration, and number of steps) of 344 cows collected between d 20 and d 120 were analyzed using restricted maximum likelihood linear mixed models with an autoregressive covariance structure. Separate models were built to include specific activities, HL status at d 120, DIM, interaction between lesion status at d 120 and DIM, parity, season of calving, and BCS change from d 20 to d 120 as fixed effects. Cow was included in all models as random effect. Incidence of HL at d 120 was 58.4% (n = 201 out of 344). Compared with healthy cows, cows with HL at d 120 had reduced daily lying duration (-0.53 h; 95% CI: -0.78 to -0.28 h) in the early postpartum period. We found no evidence for a difference in number of lying bouts (0.41; 95% CI: -0.76 to 1.59;), lying bout duration (-3.04 min; 95% CI: -6.6 to 0.49), and number of steps (62.14; 95% CI: -89.62 to 213.91) between cows that remained healthy and those that developed HL. Compared with healthy cows, cows that developed SH in 1 or more feet had reduced daily lying duration in the early postpartum period. Irrespective of lesion status at d 120, daily lying duration and lying bout duration increased from d 20 to d 120, whereas lying bout number and number of steps decreased from d 20 to d 120. We concluded that cows that developed HL had a reduced daily lying duration in the early postpartum period. Therefore, reduced daily lying duration should be considered a risk factor for HL development in lactating dairy cows.

Association between hoof lesions and fertility in lactating Jersey cows.

The objectives of this study were to evaluate the association between hoof lesions and fertility in dairy cows. Lactating Jersey cows (n = 1,639) were enrolled at 20 ± 3 d in milk (D20), examined and treated for presence of hoof lesions (HL), and evaluated for body condition score (BCS). Afterward, they were managed according to standard farm procedures, including estrus detection and presynchronization and a 5 d Cosynch-72 protocol for cows that failed to show estrus. Ovaries were scanned at 27 and 41 ± 3 d in milk, and cows with a corpus luteum greater than 20 mm on at least 1 exam were considered cyclic. At 120 ± 3 d in milk (D120), cows were re-examined for HL and BCS. Cows were classified at D20 according to HL status as healthy (n = 1,197) or having HL (n = 429), and according to HL category as healthy (n = 1,197) or having a sole hemorrhage (n = 280), noninfectious HL (sole ulcer, toe ulcer, or white line disease; n = 113), or infectious HL (digital dermatitis and foot rot; n = 36). Cows with HL at D20 had reduced odds of being cyclic (38.3 vs. 51.9%) and a longer interval from calving to first service (58 vs. 51 d) compared with healthy cows. Cows with infectious HL at D20 had reduced odds of pregnancy to first service (16.7 vs. 38.3%) compared with healthy cows. Cows with sole hemorrhage at D20 were more likely to lose pregnancies between d 32 and 64 after the first service postpartum compared with healthy cows (10.5 vs. 5.2%). Cows with sole hemorrhage at D20 had a smaller hazard of pregnancy (67.9 vs. 75.5%) at 150 d in milk and more days open (88 vs. 77d) compared with healthy cows. To assess the relationship between the development of HL and fertility, cows were classified as healthy (no HL at D20 and D120; n = 308), cured (any HL at D20 and no HL at D120; n = 72), new HL (no HL at D20 and any HL at D120; n = 597), and chronic (any HL at D20 and D120; n = 226). Sole hemorrhage accounted for 93% of new HL. The proportions of cows with HL at D20 and D120 were 26.9 and 68.4%, respectively. We found no evidence for a difference in pregnancy hazard at 150 d in milk between cows that remained healthy (n = 308) and cows that developed new HL (n = 597). Hoof lesions at D20, but not new HL, were associated with decreased odds of cyclicity, longer interval from calving to first service postpartum, and reduced pregnancy hazard in Jersey cows. The effect of an HL diagnosis in early lactation and management to reduce chronic HL in dairy cows warrants further investigation.

5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas.

INTRODUCTION: Photodynamic therapy (PDT) is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength for targeting of tumor cells. MATERIALS/METHODS: A comprehensive review of the literature was performed to analyze the indications for PDT, mechanisms of action, use of different photosensitizers, the immunomodulatory effects of PDT, and both preclinical and clinical studies for use in high-grade gliomas (HGGs). RESULTS: PDT has been approved by the United States Food and Drug Administration (FDA) for the treatment of premalignant and malignant diseases, such as actinic keratoses, Barrett's esophagus, esophageal cancers, and endobronchial non-small cell lung cancers, as well as for the treatment of choroidal neovascularization. In neuro-oncology, clinical trials are currently underway to demonstrate PDT efficacy against a number of malignancies that include HGGs and other brain tumors. Both photosensitizers and photosensitizing precursors have been used for PDT. 5-aminolevulinic acid (5-ALA), an intermediate in the heme synthesis pathway, is a photosensitizing precursor with FDA approval for PDT of actinic keratosis and as an intraoperative imaging agent for fluorescence-guided visualization of malignant tissue during glioma surgery. New trials are underway to utilize 5-ALA as a therapeutic agent for PDT of the intraoperative resection cavity and interstitial PDT for inoperable HGGs. CONCLUSION: PDT remains a promising therapeutic approach that requires further study in HGGs. Use of 5-ALA PDT permits selective tumor targeting due to the intracellular metabolism of 5-ALA. The immunomodulatory effects of PDT further strengthen its use for treatment of HGGs and requires a better understanding. The combination of PDT with adjuvant therapies for HGGs will need to be studied in randomized, controlled studies.

The temporal pattern of immune and inflammatory proteins prior to a recurrent coronary event in post-acute coronary syndrome patients.

PURPOSE: We assessed the temporal pattern of 29 immune and inflammatory proteins in post-acute coronary syndrome (ACS) patients, prior to the development of recurrent ACS. METHODS: High-frequency blood sampling was performed in 844 patients admitted for ACS during one-year follow-up. We conducted a case-control study on the 45 patients who experienced reACS (cases) and two matched event-free patients (controls) per case. Olink Proteomics' immunoassay was used to obtain serum levels of the 29 proteins, expressed in an arbitrary unit on the log2-scale (Normalized Protein eXpression, NPX). Linear mixed-effects models were applied to examine the temporal pattern of the proteins, and to illustrate differences between cases and controls. RESULTS: Mean age was 66 ± 12 years and 80% were men. Cases and controls had similar baseline clinical characteristics. During the first 30 days, and after multiple testing correction, cases had significantly higher serum levels of CXCL1 (difference of 1.00 NPX, p = 0.002), CD84 (difference of 0.64 NPX, p = 0.002) and TNFRSF10A (difference of 0.41 NPX, p < 0.001) than controls. After 30 days, serum levels of all 29 proteins were similar in cases and controls. In particular, no increase was observed prior to reACS. CONCLUSIONS: Among 29 immune and inflammatory proteins, CXCL1, CD84 and TNFRSF10A were associated with early reACS after initial ACS-admission.

Evaluation of tetracycline in milk following extra-label administration of topical tetracycline for digital dermatitis in dairy cattle.

Digital dermatitis (DD) is a painful infectious foot lesion commonly treated topically with extra-label tetracycline. Our objectives were to determine the concentrations of tetracycline in milk and plasma and to calculate a withdrawal interval following topical application at various doses. Another objective was to evaluate agreement between tests for measuring tetracycline in milk. A randomized block trial was conducted on 2 farms, where 50 cows with active DD lesions on 2 feet were allocated to 1 of 5 treatment groups (n = 10 cows per group). Treatment groups consisted of topical applications of tetracycline hydrochloride, in a paste or as a powdered form under a bandage, at 3 different dosing levels (2, 5, and 25 g) on each of the 2 affected feet. Following enrollment and treatment, samples were collected from milk, teat skin, and blood every 8 to 24 h for up to 7 d postdosing. Concentrations of tetracycline were measured by liquid chromatography-mass spectrometry and milk samples were further tested using the Charm ROSA TET test (Charm Sciences Inc., Lawrence, MA). Tetracycline was present in milk, plasma, and teat skin from all treatment groups. Tetracycline concentrations varied depending on time of sampling, method of application, and dosing level. At 8 h post-treatment, 11% of cows had tetracycline present in milk higher than 100 ng/mL (ppb) but none higher than 300 ng/mL. The 25-g treatment group had the longest estimated withdrawal interval, the highest observed concentrations (210-244 ng/mL) of tetracycline present in milk, and the longest observed consecutive period of tetracycline presence (from 8 to 72 h) among all treatment groups. Compared with liquid chromatography-mass spectrometry, the Charm test had a sensitivity of 77 and 100% for measuring tetracycline in milk at ≥30 and ≥100 ng/mL, respectively. Post-treatment samples of the teat skin were taken from 15 cows on 6 occasions, and every cow had tetracycline present in at least 1 of those 6 samples. This confirms an association between topical DD treatment with tetracycline and contamination of the teat. A total of 22% of blood samples had detectable tetracycline, and the majority (63%) occurred at 8 h post-treatment. At 100 ng/mL, the estimated cow-level milk withdrawal interval ranged from 0 to 70 h. At 300 ng/mL, the estimated cow-level withdrawal interval ranged from 0 to 34 h, and was 0 h at the bulk tank level. We recommend that conservative measures be adopted after extra-label use of topical tetracycline for DD treatment, including using a low dose and strategic post-treatment testing for tetracycline-class drugs in milk.

Evaluation of agreement among digital dermatitis scoring methods in the milking parlor, pen, and hoof trimming chute.

Digital dermatitis (DD) is the most common infectious foot lesion affecting welfare and productivity of dairy cattle. The key to DD control programs is routine and frequent identification of DD lesions. The objective was to evaluate accuracy of detecting and scoring DD lesions in 3 milking parlor designs and in 3 alternative settings compared with scoring in the hoof trimming chute as reference. A total of 552 cows and 1,104 hind feet from 17 freestall farms were scored by 1 observer in the milking parlor and in 1 other setting: pen, headlocks, or management rail. After being scored in the milking parlor and at least 1 other setting, cows were examined in the hoof trimming chute, considered the gold standard. In every setting, all hind feet were inspected visually using a flashlight and without prior washing of feet. Agreement of the scoring settings was assessed using the 5 M-stage scoring system and a dichotomous absence (M0 or M0/M1) or presence (M1 to M4.1 or M2 to M4.1) system. At trimming chute inspection, 44% of feet had a DD lesion, with estimates of 11, 5, 2, 10, and 16% for M1, M2, M3, M4, and M4.1 lesions, respectively. Apparent DD foot-level prevalence at the milking parlor, pen, management rail, and headlocks was 28, 22, 16, and 22%, respectively. M-stages were less discernible in the pen, management rail, and headlocks (apparent prevalence of M1, M2, M3, and M4.1 was ≤1%) compared with the trimming chute and milking parlor. Agreement beyond chance between any scoring setting and trimming chute scoring ranged from 0.48 to 0.70 for the dichotomous scoring system (absence = M0/M1 vs. presence = M2 to M4.1). Diagnostic test performance varied greatly among DD scoring settings but, in general, it had low sensitivity (<70%) and high specificity (>93%) for detecting any DD lesion. Agreement and test characteristics were not affected by the type of milking parlor. Although the milking parlor and headlocks were the most reliable settings in which to detect DD, none of the settings were reliable enough to replace inspection of feet in the trimming chute. However, scoring the presence or absence of DD in the milking parlor, pen, management rail, and headlocks could be used to estimate within-herd DD prevalence, to improve DD surveillance through routine monitoring, and to evaluate effects of interventions at the farm level.

Impact of the papillary muscles on cardiac magnetic resonance image analysis of important left ventricular parameters in hypertrophic cardiomyopathy.

PURPOSE: The use of cardiac magnetic resonance (CMR) analysis has increased in patients with hypertrophic cardiomyopathy (HCM). Quantification of left ventricular (LV) measures will be affected by the inclusion or exclusion of the papillary muscles as part of the LV mass, but the magnitude of effect and potential consequences are unknown. METHODS: We performed Cine-CMR in (1) clinical HCM patients (n = 55) and (2) subclinical HCM mutation carriers without hypertrophy (n = 14). Absolute and relative differences in LV ejection fraction (EF) and mass were assessed between algorithms with and without inclusion of the papillary muscles. RESULTS: Papillary muscle mass in group 1 was 6.6 ± 2.5 g/m(2) and inclusion of the papillary muscles resulted in significant relative increases in LVEF of 4.5 ± 1.8 % and in LV mass of 8.7 ± 2.6 %. For group 2 these figures were 4.0 ± 0.9 g/m(2), 3.8 ± 1.0 % and 9.5 ± 1.8 %, respectively. With a coefficient of variation of 4 %, this 9 % difference in LV mass during CMR follow-up will be considered a change, while in fact the exact same mass may have been assessed according to two different algorithms. CONCLUSIONS: In clinical HCM patients, CMR quantification of important LV measures is significantly affected by inclusion or exclusion of the papillary muscles. In relative terms, the difference was similar in subjects without hypertrophy. This underscores a general need for a uniform approach in CMR image analysis.

Observational study evaluating the association of hoof trimming with dairy cattle behavior and milk yield in Canada and the United Kingdom.

The objective of this observational study was to describe the associations between preventive hoof trimming (HT) of cows with no lesions and several behavior- and productivity-outcome measures including activity, lying behavior, and milk yield. A convenience sample of 4 freestall farms in the United Kingdom (n = 2) and Canada (n = 2) were recruited for the study. Inclusion criteria for herds included having a regular trim schedule and use of a specific pedometer system. Cows were trimmed as per their farm's regular protocol and schedule and all HT events were recorded. Only cows with no lesions present on the first recorded HT event were used in the analysis. Activity (steps/d), resting time (min/d), and resting bouts (bouts/d) were recorded daily by pedometers and total daily milk yield (kg/d) was recorded by the farm's milk recording system. Cow-level data such as DIM, breed, and parity were collected from the farm's herd management software. A generalized linear mixed repeated measures model with an exchangeable correlation structure was built to compare the outcome for 7 d following HT to baseline measures for each outcome of interest. For each outcome the average from the 5 d before HT was used as a baseline. All models included the baseline status, lactation number, season, farm, and DIM as covariates. Days from HT and its interaction with farm were included in all models. A total of 1,573 cows with no lesion recorded in their first HT were included in the analysis. Activity and resting time were inversely related on the day of HT, with activity increasing on 3 out of 4 farms (+59 to +84 steps/d) and resting time decreasing (-28 to -52 min/d). Following the day of HT, activity decreased to levels lower than those reported at baseline and resting time increased compared with baseline on most farms. There was a reduction in milk yield on the day of HT on 3 out of 4 farms and a reduction in average yield across the 7 d following trimming for all farms (range: 0.6 to 1.3 kg/d). Results were found to be farm dependent. The impact of the degree of change from baseline in behaviors and milk yield reported in this study on welfare of the cow is unclear, but the results suggest that alterations in the outcomes evaluated can persist beyond the day of trimming compared with baseline, necessitating further investigation.

Acute Coronary Syndrome Subphenotypes Based on Repeated Biomarker Measurements in Relation to Long-Term Mortality Risk.

BACKGROUND: We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long-term mortality risk. METHODS AND RESULTS: BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high-frequency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker-based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all-cause death were evaluated using accelerated failure time models (median follow-up, 9.1 years; 141 deaths). Three biomarker-based clusters were identified: cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long-term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44-0.93; P=0.018) compared with cluster 1, and 0.71 (95% CI, 0.39-1.32; P=0.281) compared with patients with a repeat ACS. CONCLUSIONS: Patients with subphenotypes of post-ACS with different all-cause mortality risks during long-term follow-up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.

Randomized clinical trial of tetracycline hydrochloride bandage and paste treatments for resolution of lesions and pain associated with digital dermatitis in dairy cattle.

Digital dermatitis is an infectious disease that causes lameness in dairy cattle, a primary welfare concern of the dairy industry. One of the common treatments for this painful hoof disease is through the application of an antibiotic bandage that must be removed following treatment. The objectives of this randomized clinical trial were to determine if topical application of tetracycline hydrochloride in a paste would be as therapeutically effective for the treatment of digital dermatitis as a powdered form of tetracycline hydrochloride held in place by a bandage, and to quantify pain associated with digital dermatitis lesions. Two hundred and fourteen Holstein cow hooves with digital dermatitis lesions were randomly assigned to 1 of 3 treatments: a tetracycline hydrochloride paste, tetracycline hydrochloride powder held in place with a bandage for 2 d, or a negative (untreated) control. Lesions were examined at 2 time periods: 3 to 7 d posttreatment and 8 to 12 d posttreatment to determine healing rates. Nociceptive thresholds were measured using a pressure algometer to quantify the pain at the lesion site. The tetracycline hydrochloride paste was as effective as the powdered bandage treatment in terms of healing rates, with 47.4 and 57.1% hooves healed at 8 to 12 d posttreatment, respectively. Both treatments were more effective than the control, in which no lesions healed 8 to 12 d following initial examination. Mean (±SE) nociceptive thresholds for active, healing, and healed lesions differed, with limb-withdrawal response occurring at 7.45 (±0.67) kg, 12.84 (±1.85) kg, and censored to 25 kg (maximum value of algometer) of force applied, respectively. However, active lesions were not consistently associated with pain, as maximum force was tolerated when applied to 19% of active lesions, perhaps due to variability in stoicism between individual cattle or due to changes in pain during the progression of infection. In conclusion, tetracycline hydrochloride paste was as effective as tetracycline hydrochloride bandage, eliminating the need for bandage removal following treatment application. Digital lesions can be painful during both active and healing stages, suggesting the need for treatment and husbandry interventions for pain mitigation.

Genetic parameters for hoof lesions and their relationship with feet and leg traits in Canadian Holstein cows.

The objectives were (1) to estimate the genetic parameters and breeding values of hoof lesions, (2) to estimate the phenotypic effect of each feet and legs conformation traits on hoof lesions, and (3) to estimate genetic correlations between hoof lesions with feet and legs conformation traits. The presence or absence of specific hoof lesions was recorded for each hoof. Lesions were classified into infectious (digital and interdigital dermatitis, foot rot, and heel erosion), horn (sole and toe ulcer, sole hemorrhage, and white line disease), and other lesions (interdigital hyperplasia, fissures, thin soles, and corkscrew claw). A total of 34,905 hoof health records from 27,179 cows and 365 herds, collected by 18 different hoof-trimmers in Ontario, Alberta, and British Columbia, were analyzed using linear animal models. In addition, 5 feet and leg conformation traits (foot angle, heel depth, bone quality, rear leg side view, and rear leg rear view) and locomotion from primiparous cows were considered (n=11,419 and 6,966 cows, for conformation traits and locomotion, respectively). At least one lesion was found in nearly 40% of the hoof trimming records. The heritability estimates for hoof lesions ranged from 0.01 for front horn lesions to 0.09 for rear infectious lesions. Despite the low heritability estimates, we observed large variability in sire estimated breeding value (EBV) for resistance to hoof lesions. Positive genetic correlations were found between the occurrence of front and rear infectious lesions (0.77) and between front and rear horn lesions (0.61), but not between infectious and horn lesions (0.08). For most of the conformation traits, low scores were phenotypically associated with higher incidence of horn lesions, whereas we found no evidence of a phenotypic effect of feet and leg traits on infectious lesions. The heritability of the conformation traits ranged from 0.04 for rear leg rear view to 0.22 for bone quality, whereas that for locomotion was 0.03. The genetic correlations between hoof lesions and conformation traits were low to moderate, yet most of the estimates were associated with high standard errors. In conclusion, although hoof lesions are lowly heritable traits, sufficient genetic variation exists (as evidenced by large variability in sire EBV) for genetic improvement through direct selection in the long term. Standardization of hoof health data collection is encouraged.

A randomized clinical trial evaluating the effects of administration of acidogenic boluses at dry-off on rumination and activity behavior in the 14 subsequent days.

Elevated milk production at dry-off can lead to increased udder pressure and, in turn, increased stress due to pain and discomfort, affecting natural behaviors. Administering acidogenic boluses at dry-off acts by inducing temporary and mild decreases in blood pH. This decreases dry matter intake, reduces milk yield, and increases cow comfort by lessening udder pressure. The objective of this study was to assess the effect of oral administration of acidogenic boluses at dry-off on total daily activity (TDA) and total daily rumination (TDR) behaviors in the first 2 wk of the dry period. This randomized clinical trial was conducted on a single farm and cows were randomly assigned to either treatment (TRT; n = 30) or control (CON; n = 34). The TRT group received 2 acidogenic boluses at dry-off and the CON group received no intervention. All cows received dry-cow therapy (intramammary antibiotic and internal teat sealant). The TDA and TDR data from 7 d before to 14 d after dry-off were measured using ear-mounted activity monitors. Analyses were performed using linear mixed-effects models with repeated measures. We observed a similar TDA in both groups throughout the study follow-up period. Overall, cows in the TRT group spent 17 min/d less time active than cows in the CON group in the first 2 wk after dry-off with the greatest difference observed on the second day of the dry period (TRT = 395 min/d; 95% CI: 370 to 420 vs. CON = 428 min/d; 95% CI: 404 to 451). The TRT group had lower TDR in the first 24 h after bolus administration (TRT = 437 min/d; 95% CI: 414 to 461 vs. CON = 488 min/d; 95% CI: 466 to 510) when compared with the CON group, but no differences were observed when comparing both groups in the 13 subsequent days. Our results indicate that administering acidogenic boluses at dry-off slightly decreased TDA during the first 2 wk of the dry period and decreased TDR on the first day after administration.

Association between engagement in exercise training and peak cardiac biomarker concentrations following ST-elevation myocardial infarction.

Background: Regular exercise training is an important factor in prevention of myocardial infarction (MI). However, little is known whether exercise engagement prior to MI is related to the magnitude of post-MI cardiac biomarker concentrations and clinical outcomes. Objectives: We tested the hypothesis that exercise engagement in the week prior MI is related to lower cardiac biomarker concentrations following ST-elevated MI (STEMI). Methods: We recruited hospitalised STEMI patients and assessed the amount of exercise engagement in the 7 days preceding MI onset using a validated questionnaire. Patients were classified as 'exercise' if they performed any vigorous exercise in the week prior MI, or as 'control' if they did not. Post-MI peak concentrations of high-sensitive cardiac troponin T (peak-hs-cTnT) and creatine kinase (peak-CK) were examined. We also explored whether exercise engagement prior MI is related to the clinical course (duration of hospitalisation and incidence of in-hospital, 30-day and 6-month major adverse cardiac events (reinfarction, target vessel revascularisation, cardiogenic shock or death)). Results: In total, 98 STEMI patients were included, of which 16% (n=16) was classified as 'exercise', and 84% (n=82) as 'control'. Post-MI peak-hs-cTnT and peak-CK concentrations were lower in the exercise group (941 (645-2925) ng/mL; 477 (346-1402) U/L, respectively) compared with controls (3136 (1553-4969) ng/mL, p=0.010; 1055 (596-2019) U/L, p=0.016, respectively). During follow-up, no significant differences were found between both groups. Conclusion: Engagement in exercise is associated with lower cardiac biomarker peak concentrations following STEMI. These data could provide further support for the cardiovascular health benefits of exercise training.