The aim of this study was to determine the association between concentrations of progesterone (P4) during previous the estrous cycle with the intensity of spontaneous or estrogen-induced estrous ...expression and pregnancy per artificial insemination (P/AI). A total of 1,953 AI events from lactating Holstein cows were used, consisting of 1,289 timed AI events from experiment 1 (Exp. 1) and 664 AI events from experiment 2 (Exp. 2). In Exp. 1, cows were bred after a timed AI protocol based on estradiol and P4. In Exp. 2 animals were bred upon spontaneous estrus detection. In both experiments cows were continuously monitored by an automated activity monitor (AAM), in Exp.1 a relative increase of activity was calculated (i.e., percentage of increase activity at estrus compared to cow's baseline activity) and in Exp.2, activity data from each cow were computed into an index value that ranged from 0 to 100. In Exp.2 duration (hours) of estrus were calculated and defined as the total time above the threshold (35 index). The intensity of estrous expression was determined for each event and classified as either high or low intensity using the median of each experiment. Blood samples were collected for P4 analysis in Exp. 1 at -4 d, 0 d, and 7 d relative to timed AI, and in Exp. 2 immediately following estrus (0 d), 7 d, 14 d, and 21 d post-AI. Concentration of P4 was classified as greater or lower according to the median value in each experiment. Cows with lower concentrations of P4 at AI had greater estrous expression in Exp. 1 (363.6 ± 5.2 vs. 275.9 ± 8.0% relative increase) and Exp. 2 (76.7 ± 1.9 vs. 67.4 ± 4.7 index; and 12.5 ± 0.5 vs. 9.3 ± 1.8 hours). Cows with a greater intensity of estrous expression at timed AI had greater concentrations of P4 at -4 d than cows with lower intensity estrus or no estrous expression (4.6 ± 0.2 vs. 3.6 ± 0.2 vs. 3.7 ± 0.2 ng/mL). Cows with greater concentrations of P4 at -4 d had greater P/AI (32.8 ± 4.4 vs. 22.4 ± 4.5%), whereas cows with lesser concentrations of P4 at d0 for either timed AI (35.2 ± 3.4 vs. 19.6 ± 4.6%) or spontaneous estrus (31.8 ± 2.8 vs. 23.4 ± 3.2%) had greater P/AI. Cows with greater concentrations of P4 7 d post-timed AI had greater P/AI compared with cows that had lower concentration of P4 (39.1 ± 2.9 vs. 24.7 ± 2.6%). Similarly, cows that had lower concentrations of P4 at 7 d, 14 d and 21 d post-spontaneous estrus tended to have lower P/AI when compared with cows with greater concentrations of P4. Overall, concentrations of P4 prior to and at AI were associated with greater estrous intensity and P/AI at both spontaneous and timed AI events.
Processing of whey proteins yields several bioactive peptides that can trigger physiological effects in the human body: on the nervous system via their opiate and ileum-contracting activities; on the ...cardiovascular system via their antithrombotic and antihypertensive activities; on the immune system via their antimicrobial and antiviral activities; and on the nutrition system via their digestibility and hypocholesterolemic effects. The specific physiological effects, as well the mechanisms by which they are achieved and the stabilities of the peptides obtained from various whey fractions during their gastrointestinal route, are specifically discussed in this review.
The objective of this study was to determine risk-factors affecting increase in physical activity during estrus and pregnancy per artificial insemination (P/AI) in lactating dairy cows. Cows were ...monitored continuously by 2 automated activity monitors a collar-mounted accelerometer (HT; Heatime, SCR Engineers, Netanya, Israel) and a leg-mounted pedometer (BO; Boumatic Heat-seeker-TX, Boumatic Dairy Equipment, Madison, WI). When an increase in activity was detected, body condition score (BCS) and blood samples were collected, ovaries were scanned by ultrasonography, and, if the cow was eligible for breeding, artificial insemination was performed. Milk production and health-related data were recorded throughout the experimental period. Pregnancy diagnosis was performed at 42±7 d of gestation. Data were analyzed using Pearson correlation, ANOVA, and logistic regression. A total of 1,099 true events of estrus from 318 lactating Holstein cows were recorded, averaging 3.46±1.1 events per cow. Positive predictive value for estrus episodes detected by the HT and BO systems were 89.6 and 85.5%, respectively. Mean peak activity at estrus (PA) recorded by the HT system was 71.6±20.7 index-value, and 334.3±155.7% relative increase by the BO system. Compared with primiparous, multiparous cows expressed estrus with lower PA (69.3±0.8 vs. 75.9±1.1 index for HT; 323.9±6.0 vs. 354.8±8.48% for BO) and shorter duration (DU; 10.7±0.2 vs. 12.0±0.3 h); DU was measured by HT only. Lower BCS was associated with decreased PA measured by both systems, estrus DU, and P/AI. Peak activity was weakly correlated with milk production on the day of artificial insemination (r=−0.20); however, when categorized into quartiles, the highest-yield cows had lower PA and DU. Follicle diameter was not correlated with PA or DU, but cows with greater concentrations of estradiol had higher PA. Cows with greater PA in both systems had greater P/AI than those with lower PA (36.5 vs. 24.6% for HT, 33.5 vs. 21.4% for BO). In conclusion, measurements of estrus events captured by automated activity monitors are correlated with BCS, parity, and secondary behavior signs related to estrus. Surprisingly, estrus intensity and duration were only weakly correlated with milk production, preovulatory follicle diameter, and concentrations of estradiol at estrus. Cows that had measurements of high-intensity estrus were significantly more fertile than low-intensity estrus.
The objective of this study was to evaluate the effects of the use of intravaginal probiotics prepartum on the incidence risk of metritis postpartum and conception risk after first artificial ...insemination (AI). A total of 606 Holstein cows were enrolled 3 wk before their expected calving date from 2 farms. Cows were randomly assigned to either receive a 2-mL dose of a combination of 3 lactic acid bacteria (probiotic treatment) washed with approximately 2 mL of a sterile saline solution, into the vaginal canal twice weekly until parturition, or no intervention (control). Metritis diagnoses were carried out on 6 and 12 d postpartum. Vaginal discharge and rectal temperature were assessed, and vaginal discharge was scored on a scale from 1 to 4, where 1 = clear and 4 = fetid, purulent discharge. Metritis was defined as cows having a vaginal discharge score of 4 with or without fever (rectal temperature ≥39.5°C) on either 6 or 12 d postpartum, or both. Cows were bred after a 60-d voluntary waiting period primarily via the detection of estrus using automated activity monitors; cows not found in estrus were enrolled onto timed AI protocols to receive first breeding before 100 DIM. Pregnancy diagnosis was carried out at d 35 ± 7 post-AI on both farms. Data were analyzed via ANOVA using linear mixed regression models and survival analysis using a Cox proportional hazard model. Total incidence risk of metritis was 23.7% and 34.4% on farm A and farm B, respectively. Overall, the incidence of metritis was not different between treatment groups (control: 41.6 ± 3.8%; probiotic: 38.6 ± 4.0%); however, an interaction by farm was detected, where the probiotic treatment reduced metritis on one farm but not on the other. Conception risk after first AI was not affected by treatment. However, we detected an interaction between parity and treatment, where multiparous cows receiving the probiotic treatment were more likely to become pregnant compared with multiparous cows within the control group (hazard ratio: 1.33; 95% confidence interval: 1.10–1.60); no effect of probiotic treatment was found on the hazard of pregnancy for primiparous cows. In addition, the probiotic treatment was associated with an increased proportion of cows being detected in estrus for the first AI postpartum. In conclusion, vaginal probiotic treatment applied during the 3 wk prepartum was associated with a decreased incidence of metritis on one farm but not the other, suggesting that farm management may be a key player influencing treatment efficacy. Overall, probiotic treatment was found to have only limited effects on fertility in the current study.
The objective of this observational study was to identify factors associated with estrous duration (DU) and intensity measured as the peak of activity (PA) change and subsequent fertility in ...lactating Holstein cows using a neck-mounted automated activity monitor (Heatime Pro, SCR Engineers Ltd., Netanya, Israel). Ambient temperature and relative humidity were recorded hourly to calculate the temperature-humidity index (THI). A total of 5,933 estrus events from 3,132 cows located on 8 commercial dairy farms in Germany were used for this study. Farms participated in monthly DHIA testing. Pregnancy diagnosis was performed either by transrectal palpation farm 1: 42 ± 3 d; farm 3: 40 ± 3 d; farms 4 and 8: 38 ± 3 d; farm 5: 43 ± 3 d after artificial insemination (AI) or transrectal ultrasonography (farms 2, 6, and 7: 30 ± 3 d after AI). Estrous intensity was categorized based on peak activity of estrus into low (35–89 index value), and high (90–100 index value) PA. Overall, 73.5% of estrus events were of high PA. The mean (± standard error of the mean) DU was 14.94 ± 0.06 h. There was a strong correlation between DU and PA (r = 0.67). In the final statistical model, only PA was associated with pregnancy per artificial insemination (P/AI), with 1.35 greater odds of pregnancy for cows with high PA compared with cows with low PA. Increased THI 1 wk before AI was associated with shorter DU, lower PA, and decreased P/AI. A small percentage of cows (4.7%) showed short interestrus intervals (i.e., more than 1 activity peak within 7 d close to the event of estrus), resulting in reduced DU, PA, and P/AI. The change of weighted rumination was associated with DU and PA, as a lower nadir was associated with a greater risk for high PA and long DU. There was no association, however, between the nadir of change of weighted rumination and P/AI. Whereas milk yield and somatic cell count from the DHIA test date before AI were negatively associated with estrous expression, neither milk yield nor somatic cell count was associated with P/AI. Surprisingly, multiparous cows expressed estrus with longer DU (13.15 ± 0.31 h) compared with primiparous cows (12.52 ± 0.32 h), whereas PA did not differ among parities. Pregnancy per AI was greater for primiparous (29.4%) than for multiparous (22.1%) cows. An estrus event with long DU or high PA was more likely later in lactation. Milk fat, milk protein, milk urea nitrogen, and lactose from the DHIA test date closest to AI had no association with estrous expression or P/AI. In conclusion, DU and PA were highly correlated, and cows with high PA were particularly associated with greater odds for pregnancy. A negative association between estrous expression and P/AI was identified for increased THI 1 wk before AI and cows with short interestrus intervals using automated activity monitor.
The objectives of this retrospective observational study were to determine the associations of anogenital distance (AGD) with (a) postpartum estrous activity, (b) diameter of the preovulatory ...follicle, (c) intensity of estrous expression, (d) postestrus ovulation, (e) corpus luteum (CL) size, and (f) concentrations of progesterone at estrus and on d 7 after estrus. Lactating Holstein cows (n = 178; 55 primiparous, 123 multiparous) were enrolled into the study during the first postpartum week. All cows were continuously monitored by a pedometer-based automated activity monitoring (AAM) system for estrus. Postpartum estrous activity was assessed using the AAM estrus alerts, in which cows with at least one true estrus alert (i.e., a relative increase in steps from each cow's baseline detected by the AAM and the presence of at least one follicle >15 mm, a CL <20 mm, or no CL detected by ultrasound) by the first 50 d in milk (DIM) were considered to have commenced estrous activity. At the estrus alert >60 DIM, ovulation was determined by ultrasound at 24 h, 48 h, and 7 d after estrus, and blood samples were collected at estrus alert and on d 7 after estrus for progesterone analysis. The AGD was measured from the center of the anus to the base of the clitoris and classified as either short- or long-AGD using 2 cut-points of 148 mm (predictive of the probability of pregnancy to first insemination; short-AGD, n = 115; long-AGD, n = 63) and 142 mm (the median AGD; short-AGD, n = 90; long-AGD, n = 88). Regardless of the cut-point used, early postpartum estrous activity by 50 DIM (67 vs. 54%), duration of estrus (11.6 vs. 9.7 h), and preovulatory follicle diameter (20 vs. 19 mm) were greater in short-AGD than in long-AGD cows. Increased peak of activity at estrus in short-AGD cows (354 vs. 258% mean relative increase) was affected by an interaction between AGD and parity in which multiparous long-AGD cows had lesser relative increase in activity than primiparous cows (217 vs. 386%, respectively). Mean progesterone concentration at estrus was lesser in short-AGD (0.47 vs. 0.61 ng/mL) than in long-AGD cows. The ovulatory response at 24 h did not differ, but at 48 h (91 vs. 78%) and on d 7 after estrus (97 vs. 84%) it was greater in short-AGD cows. Although CL diameter on d 7 after estrus did not differ, short-AGD cows had greater progesterone concentration 7 d after estrus than long-AGD cows (4.1 vs. 3.2 ng/mL, respectively). In conclusion, greater proportions of short-AGD cows commenced estrous activity by 50 DIM, had larger preovulatory follicles, exhibited greater duration of estrus, had reduced progesterone concentration at estrus, had greater ovulation rates and progesterone concentration 7 d after estrus compared with long-AGD cows, with no difference in CL size between AGD groups. Because all the differences in physiological characteristics of short-AGD cows reported herein favor improved reproductive outcomes, we infer that these are factors contributing to improved fertility reported in short-AGD cows compared with long-AGD cows.
The objective of this observational study was to evaluate the relationship between genomic daughter pregnancy rate (GDPR) with reproduction parameters such as pregnancy at first artificial ...insemination (AI), pregnancy per AI, and pregnancy losses (PL). A total of 12,949 events from 3,499 Holstein cows were included. Cows were enrolled as nulliparous (n = 1,220), primiparous (n = 1,314), or multiparous (n = 965). Cows were bred either after a timed AI protocol, timed embryo transfer (ET), or spontaneous estrus. Most lactating cows were bred following a timed AI protocol based on estradiol and progesterone, and most nulliparous were artificially inseminated following estrus detection. Hair samples were collected from the tail switch and cows were genotyped using a SNP platform (Clarifide, Zoetis). Cows that were bred by timed AI were evaluated for estrous behavior using tail chalk. Tail chalk was applied on the head of the tail 2 d before timed AI and the chalk was evaluated at AI (no estrus: 100% of chalk remaining or ≥50% of chalk remaining; Estrus: <50% of chalk remaining). Pregnancy diagnosis was performed at d 32 and 60 after AI using ultrasonography, and the presence of a heartbeat was considered a positive diagnosis. Pregnancy loss was defined as a pregnant cow on d 32 that was nonpregnant on d 60. As GDPR increased, the odds of pregnancy at first AI increased odds ratio (OR) = 1.28, 95% CI = 1.20–1.35, the odds of pregnancy per AI increased (OR = 1.31, 95% CI = 1.25–1.36), and the odds of PL decreased (OR = 0.66, 95% CI = 0.60–0.72). Most cows that were bred on the day of the timed AI demonstrated estrus (n = 6,075; 92.9%). The odds of demonstrating estrus on the day of timed AI increased as GDPR increased (OR = 1.31, 95% CI = 1.17–1.48). There was no interaction between GDPR and parity or breeding management for pregnancy at first AI, pregnancy per AI, and PL. In conclusion, the odds of pregnancy at first AI and pregnancy per AI increased as GDPR increased. Moreover, the odds of PL increased as GDPR decreased. Greater GDPR was also associated with greater occurrence of estrus on the day of timed AI. These results suggest that selecting for higher GDPR could result in better reproductive performance, but this would need to be assessed with additional research.
The objective of this study was to examine the association between increased physical activity at the moment of timed artificial insemination (AI), detected by an automated activity monitor (AAM), ...and fertility outcomes. This paper also investigated factors affecting estrous expression in general. A total of 1,411 AI events from 1,040 lactating Holstein cows were recorded, averaging 1.3 ± 0.6 (±standard deviation) events per cow. Activity (measured as steps/h) was monitored continuously by a leg-mounted AAM located on the rear leg of the cow. Ovulation was synchronized by a timed AI protocol based on estradiol and progesterone. Ovarian ultrasonography was performed in all cows on d −11 (AI = d 0) and in a subset of cows on d 0 (n = 588) and d 7 (n = 819) to determine the presence of a corpus luteum and follicles. The body condition score (1 to 5 scale) was assessed on d 0 and a blood sample was collected for progesterone measurement on d 7. Using the AAM, an estrus event was determined when the relative increase (RI) in physical activity of the cow exceeded 100% of the baseline activity. The physical activity was classified as strong RI (≥300% RI), moderate RI (100–300% RI), or no estrus (<100% RI). Milk production was measured daily and averaged between d −11 and 0. Pregnancy was diagnosed at 32 and 60 d post-AI and pregnancy losses were calculated. The mean RI at estrus was 328.3 ± 132.1%. Cows with strong RI had greater pregnancy per AI than those with moderate RI and those that did not express estrus (35.1 vs. 27.3 vs. 6.2%). When including only cows that successfully ovulated after timed AI, those that displayed strong intensity RI still had greater pregnancy per AI than those with moderate intensity RI or those that did not express estrus (45.1 vs. 34.8 vs. 6.2%). Cows expressing strong RI at timed AI had greater ovulation rates compared with moderate RI and cows that did not express estrus (94.9 vs. 88.2 vs. 49.5%). Furthermore, pregnancy losses were reduced in cows with strong RI compared with cows expressing moderate RI (13.9 vs. 21.7%). Cows with a strong RI at estrus were more likely to have a corpus luteum at the beginning of the protocol and had greater concentration of progesterone 7 d post-AI. Multiparous cows expressed lower RI compared with primiparous cows. Cows with lower body condition score tended to have decreased RI at estrus. No correlation between estrous expression and pre-ovulatory follicle diameter was observed. Also, no correlation was observed between milk production at AI and RI. In conclusion, strong intensity RI of estrus events at timed AI was associated with improved ovulation rates and pregnancy per AI, and reduced pregnancy losses. These results provide further evidence that measurements of estrous expression can be used to predict fertility at the time of AI and possibly be used as a tool to assist decision making strategies of reproduction programs.
We describe 70 children with myelodysplastic syndrome (MDS) (refractory cytopenia (n=31) and refractory anemia with excess blasts (n=30) or blasts in transformation (n=9)) who received umbilical cord ...blood (UCB) transplantation with a single UCB unit and a myeloablative conditioning regimen. Approximately 20% of children had secondary MDS. Median age at transplantation was 7 years and the median follow-up was 3 years. The day-60 probability of neutrophil recovery was 76%; recovery was faster after transplantation of matched or 1-locus mismatched UCB, irradiation-containing conditioning regimen, cell dose >6 × 10(7)/kg and monosomy 7. Risks of treatment failure (recurrent disease or death) were lower in patients with monosomy 7 and transplantations after 2001. The 3-year disease-free survival (DFS) was 50% for transplantations after 2001 compared with 27% for the earlier period (P=0.018). Transplantations after 2001 occurred within 6 months after diagnosis and used UCB units with higher cell dose. DFS was highest in patients with monosomy 7 (61%) compared with other karyotypes (30%), P=0.017. These data suggest that transplantation of mismatched UCB graft is an acceptable alternative for children without a matched sibling or suitably matched unrelated adult donor.
Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple ...types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (
<0.001 for global cognitive function, processing speed, executive functions, and memory and
<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on
scores strongly predicted cognitive and functional outcomes (
<0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.
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