The objective was to assess gait, automated measures of weight distribution among the legs, and daily activity as methods for detecting lameness in dairy cows and measuring pain mitigation by nonsteroidal antiinflammatory drugs. Fifty-seven lactating cows (28 of which were lame) were injected twice with ketoprofen (3.0 mg/kg i.m.) or isotonic saline solution. Gait scores (numerical rating system, NRS), time spent lying down, frequency of steps, and weight distribution among legs when standing before, during, and after injections were measured to assess whether automated measures of activity can detect lameness and the effect of analgesic drugs in cows. Lame cows (NRS >3) shifted weight between contralateral legs more often (SD of the weight applied: 31.1+/-2.1 vs. 24.5+/-1.9kg), had a greater asymmetry in the weight applied to the rear legs (leg weight ratio=0.78+/-0.02 vs. 0.87+/-0.02), had longer lying bouts (94.0+/-4.9 vs. 78.2+/-5.8min), and walked slower (1.28+/-0.3 vs. 1.42+/-0.3 m/s) than nonlame cows. Variability over time (SD) of the weight applied to the rear legs was the most accurate predictor of whether a cow was lame or not (area under the curve=0.71). The SD of the weight applied to the rear legs decreased on the days when ketoprofen was given compared with the day before and after (18 and 12% decrease for lame and nonlame cows, respectively). Ketoprofen did not affect any other measure. Measures of weight shifting between legs while cows are standing have potential as an automated method of detecting lameness and analgesia.

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Results provide information on current attitudes and practices related to pain and analgesia in cattle among US veterinarians in bovine practice and can be considered in the development of policies and protocols for pain management in cattle. These data can be compared with those of future studies to examine changes over time.

Mastitis is a frequent and painful disease in dairy cows. However, pain detection and alleviation in mastitic cows has been overlooked. The objectives of this study were to measure behavioral changes in dairy cows with clinical mastitis and to investigate the effect of intramammary infusion of an antibiotic on lying behavior and behavior during milking. In experiment 1, 42 lactating cows were used: 14 mastitic cows and 28 control cows. Mastitic and control cows were subjected to an evaluation of pain responses on d 1 (mastitis detection day), and 2, 3, and 7d after the last antibiotic treatment (d 10+). The antibiotic treatment was administered to mastitic cows twice a day, starting on d 1, for at least 3 consecutive days. Behavioral changes were evaluated by measuring lying behavior, reactivity during milking (stepping, lifting, and kicking), weight distribution, and hock-to-hock distance. Overall, mastitic cows spent less time lying down on d 2 compared with control cows. The percentage of time lying on the mastitic quarter side did not differ significantly between mastitic and control cows. No differences were observed between control and mastitic cows on the number of steps per 24h on each day. Restless behavior during milking did not differ between treatments. Restless behaviors differed significantly within mastitic cows between days. Frequency of kicks per minute was higher on d 1 compared with d 2, frequency of lifts was higher on d 1 and 2 compared with d 10+, and frequency of steps was higher on d 2 compared with d 10+. The variability of weight that mastitic cows applied to the leg on the mastitic quarter side was higher on d 1 than on d 10+. For control cows, the variability in weight applied to the homologous leg of the mastitic quarter side leg was higher on d 1 compared with d 2 and 3. The hock-to-hock distance did not differ between treatments. Mild clinical mastitis might not cause sufficient pain to observe marked changes in behaviors. However, cows showed differences in lying time and reactivity during milking and slight differences in the laterality of lying. To further develop methodologies for assessing pain in mastitic cows, it is worth applying the methodologies used in this study to cows with moderate to severe mastitis, followed by their validation using analgesic treatment, to ensure that any change is a pain-specific behavior rather than a simple reflex. In experiment 2, no effect of intramammary infusion of the antibiotic was observed on lying behavior or behavior during milking. Cows with mild clinical mastitis present behavioral changes in lying behavior and at milking time, which could be associated with discomfort.

Background The authors investigated the durability of vaccine efficacy (VE) against human papillomavirus (HPV)16 or 18 infections and antibody response among nonrandomly assigned women who received a single dose of the bivalent HPV vaccine compared with women who received multiple doses and unvaccinated women. Methods HPV infections were compared between HPV16 or 18-vaccinated women aged 18 to 25 years who received one (N = 112), two (N = 62), or three (N = 1365) doses, and age- and geography-matched unvaccinated women (N = 1783) in the long-term follow-up of the Costa Rica HPV Vaccine Trial. Cervical HPV infections were measured at two study visits, approximately 9 and 11 years after initial HPV vaccination, using National Cancer Institute next-generation sequencing TypeSeq1 assay. VE and 95% confidence intervals (CIs) were estimated. HPV16 or 18 antibody levels were measured in all one- and two-dose women, and a subset of three-dose women, using a virus-like particle-based enzyme-linked immunosorbent assay (n = 448). Results Median follow-up for the HPV-vaccinated group was 11.3 years (interquartile range = 10.9–11.7 years) and did not vary by dose group. VE against prevalent HPV16 or 18 infection was 80.2% (95% CI = 70.7% to 87.0%) among three-dose, 83.8% (95% CI = 19.5% to 99.2%) among two-dose, and 82.1% (95% CI = 40.2% to 97.0%) among single-dose women. HPV16 or 18 antibody levels did not qualitatively decline between years four and 11 regardless of the number of doses given, although one-dose titers continue to be statistically significantly lower compared with two- and three-dose titers. Conclusion More than a decade after HPV vaccination, single-dose VE against HPV16 or 18 infection remained high and HPV16 or 18 antibodies remained stable. A single dose of bivalent HPV vaccine may induce sufficiently durable protection that obviates the need for more doses.

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BRCA1 is a breast cancer susceptibility gene that is downregulated in a significant proportion of sporadic breast cancers. BRCA1 is posttranscriptionally regulated by RNAbinding proteins, the identities of which are unknown. HuR is an RNA binding protein implicated in posttranscriptional regulation of many genes and is overexpressed in sporadic breast cancer. To investigate the possibility that these two molecules are functionally linked in breast cancer, we performed bioinformatic analysis of the BRCA1 3 ¶ untranslated region (UTR), RNA-protein assays with the HuR protein and the BRCA1 3 ¶UTR, and immunohistochemical analysis of a cohort of breast tumors using antibodies against BRCA1 and HuR. Here, we describe the identification of two predicted HuR-binding sites in the BRCA1 3 ¶UTR, one of which binds specifically to HuR. We also show that this interaction is disrupted by single nucleotide substitutions in the BRCA1 3 ¶UTR and that endogenous HuR protein associates with BRCA1 transcripts in T47D and MCF7 breast cancer cells. Expression of ectopic HuR results in a significant decrease in BRCA1 protein expression and also BRCA1 3 ¶UTR activity. Immunohistochemical analysis revealed that although BRCA1 and HuR expression were associated with some clinicopathologic features of the tumors, there was no statistically significant correlation between BRCA1 and HuR protein expression. These results identify the first posttranscriptional protein regulator of BRCA1 and have implications for understanding BRCA1 regulation in human breast cancer. [Cancer Res 2008;68(22):9469-78]

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