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Magnetic resonance imaging (MRI) examinations were performed in 15 patients with musculoskeletal neoplasms to assess the value of magnetization transfer contrast in tumor characterization. Multiplanar gradient-recalled echo sequences (TR 500-600/TE 15-20/flip angle 20-30 degrees) were performed first without and then with magnetization transfer contrast generated by a zero degree binomial pulse (MPGR and MTMPGR). Standard T1-weighted spin echo images (SE; TR 300-400/TE 12-20) and either T2-weighted SE (TR 2000-2900/TE 70-80) or T2-weighted fast spin echo (FSE; TR 4000-5000/TE 100-119 effective) images were also obtained. Signal intensities on MTMPGR scans were compared to those on MPGR scans for both tumors and normal tissues. Signal intensity ratios (SIR) and contrast-to-noise ratios (CNR) were also compared for all sequences. MTMPGR images provided better contrast between pathologic tissues and muscle than did standard MPGR images, increasing both conspicuity of lesions and definition of tumor/muscle interfaces. Benign and malignant tumors, with the exception of lipoma, underwent similar degrees of magnetization transfer and could not be distinguished by this technique. [ABSTRACT FROM AUTHOR]

A task was developed to study the generalization of a prohibition in preschool children as a function of amount of information given them. Ss were given a supply of building blocks, some of which they were free to use and some of which were forbidden. One-half of the Ss were given explicit information about the characteristics of the forbidden blocks, while for the other half of the Ss the forbidden blocks were identified but their distinctive features were not pointed out. Ss were then given a different, but similar, set of blocks and were asked to put aside the forbidden ones. It was hypothesized that Ss with specific information would generalize appropriately to the new set of blocks, while those without such information would generalize on the basis of irrelevant stimulus features. The hypothesis was supported. [ABSTRACT FROM AUTHOR]

Osteoporosis is a disorder characterized by osteoclastic dysfunction. The bones of afflicted patients become sclerotic and show modeling defects resulting in either a decrease or obliteration of the marrow cavity and resultant pancytopenia. Other clinical manifestations include bony deformities, cranial nerve palsies from bony overgrowth, pathological fractures, osteomyelitis, and hepatosplenomegaly secondary to extramedullary hematopoiesis. In the skull, the diploic space is usually decreased or obliterated. Absent or decreased marrow space is observed on plain films. On MRI, the marrow cavity very likely will be obliterated with low signal intensity on T1- and T2-weighted images. We report a case of osteopetrosis in which the diploic space is markedly increased, giving a hair-on-end appearance resembling thalassemia major. Perhaps some local factor within the diploic space prevented the expected osteoclastic dysfunction, allowing remodeling and expansion of the cranial vault. [ABSTRACT FROM AUTHOR]

Energy balance (EB) and energy intake (EI) are heritable traits of economic importance. Despite this, neither trait is explicitly included in national dairy cow breeding goals due to a lack of routinely available data from which to compute reliable breeding values. Mid-infrared (MIR) spectrometry, which is performed during routine milk recording, is an accurate predictor of both EB and EI. The objective of this study was to estimate genetic parameters of EB and EI predicted using MIR spectrometry. Measured EI and EB were available for 1,102 Irish Holstein-Friesian cows based on actual feed intake and energy sink data. A subset of these data (1,270 test-day records) was used to develop equations to predict EI, EB, and daily change in body condition score (ΔBCS) and body weight (ΔBW) using the MIR spectrum with or without milk yield also as a predictor variable. Accuracy of cross-validation of the prediction equations was 0.75, 0.73, 0.77, and 0.70 for EI, EB, ΔBCS, and ΔBW, respectively. Prediction equations were applied to additional spectral data, yielding up to 94,653 records of MIR-predicted EI, EB, ΔBCS, and ΔBW available for variance component estimation. Variance components were estimated using repeatability animal linear mixed models. Heritabilities of MIR-predicted EI, EB, ΔBCS, and ΔBW were 0.20, 0.10, 0.07, and 0.06, respectively; heritability estimates of the respective measured traits were 0.35, 0.16, 0.07, and 0.08, respectively. The genetic correlation between measured and MIR-predicted EI was 0.84 and between measured and MIR-predicted EB was 0.54, indicating that selection based on MIR-predicted EI or EB would improve true EI or EB. Genetic and phenotypic associations between EI and both the milk production and body-change traits were generally in agreement, regardless of whether measured EI or MIR-predicted EI was considered. Higher-yielding animals of higher body weight had greater EI. Predicted EB was negatively genetically correlated with milk yield (genetic correlation = -0.29) and positively genetically correlated with both milk fat and protein percent (genetic correlation = 0.17 and 0.16, respectively). Least squares means phenotypic EI of 198 animals stratified as low, average, and high estimated breeding values for MIR-predicted EI (animal phenotypes were not included in the genetic evaluation) were 154.3, 156.0, and 163.3 MJ/d, corroborating that selection on MIR-predicted EI will, on average, result in differences in phenotypic true EI. [ABSTRACT FROM AUTHOR]

Interest is increasing in the feed intake complex of individual dairy cows, both for management and animal breeding. However, energy intake data on an individual-cow basis are not routinely available. The objective of the present study was to quantify the ability of routinely undertaken mid-infrared (MIR) spectroscopy analysis of individual cow milk samples to predict individual cow energy intake and efficiency. Feed efficiency in the present study was described by residual feed intake (RFI), which is the difference between actual energy intake and energy used (e.g., milk production, maintenance, and body tissue anabolism) or supplied from body tissue mobilization. A total of 1,535 records for energy intake, RFI, and milk MIR spectral data were available from an Irish research herd across 36 different test days from 535 lactations on 378 cows. Partial least squares regression analyses were used to relate the milk MIR spectral data to either energy intake or efficiency. The coefficient of correlation (REX) of models to predict RFI across lactation ranged from 0.48 to 0.60 in an external validation data set; the predictive ability was, however, strongest (REX = 0.65) in early lactation (<60 d in milk). The inclusion of milk yield as a predictor variable improved the accuracy of predicting energy intake across lactation (REX = 0.70). The correlation between measured RFI and measured energy balance across lactation was 0.85, whereas the correlation between RFI and energy balance, both predicted from the MIR spectrum, was 0.65. Milk MIR spectral data are routinely generated for individual cows throughout lactation and, therefore, the prediction equations developed in the present study can be immediately (and retrospectively where MIR spectral data have been stored) applied to predict energy intake and efficiency to aid in management and breeding decisions. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the incidence and timing of pregnancy loss from service event (timed artificial insemination or timed embryo transfer) to parturition. Lactating Holstein-Friesian cows were randomly assigned to receive either artificial insemination (AI, n = 243) or embryo transfer (ET, n = 863) with a fresh or frozen in vitro-produced blastocyst derived from oocytes collected from the ovaries of elite dairy donors (n = 14 Holstein Friesian and n = 8 Jersey) and elite beef donors (n = 21 Angus) using transvaginal ovum pick-up. In addition, oocytes were collected from the ovaries of beef heifers of known pedigree following slaughter at a commercial abattoir (n = 119). Blood samples were collected on d 7 from all cows to determine progesterone concentration and from subsets of cows on d 18 (n = 524) and d 25 (n = 378) to determine mRNA abundance of interferon-stimulated gene-15 and pregnancy-specific protein B concentration, respectively, to provide an early pregnancy diagnosis. Transrectal ultrasonography was conducted to determine pregnancy status on d 32, d 62 and d 125 after synchronized ovulation. Parturition date was recorded for all cows that reached a term delivery. The predicted probability of pregnancy (%) varied at each time point (d7, 18, 25, 32, 62, 125, parturition) depending on treatment (AI: 77.0, 60.2, 52.3, 48.8, 47.0, 44.6, 44.0; fresh ET: 100.0, 69.5, 60.3, 56.1, 48.4, 46.8, 45.5; frozen ET: 100.0, 61.7, 52.2, 41.6, 32.9, 31.8, 30.2). Irrespective of treatment, the largest proportion of pregnancy loss occurred in the period from service event (AI on d 0 or ET on d 7) to d 18, with minimal loss occurring between d 62 and parturition (AI: 1.8%, fresh ET: 1.9%, frozen ET: 3.5%). Treatment differences in the predicted probability of pregnancy per service event were detected between fresh ET vs frozen ET on d 32 and both AI and fresh ET vs frozen ET on d 62, 125 and at parturition. There was greater probability of pregnancy loss between d 32 and 62 following ET (Fresh: 11.3%, Frozen: 18.0%) than AI (4.0%). The percentage of cows that calved following transfer of a fresh embryo (45.5%) was similar to AI (44.0%), but less when a frozen embryo was transferred (30.2%). In conclusion, AI and fresh ET led to a greater probability of a cow becoming pregnant and maintaining the pregnancy to term than frozen ET. Cows that were still pregnant on d 62 had a very strong likelihood of maintaining the pregnancy to full-term parturition, irrespective of treatment. Further work is required to improve the likelihood of pregnancy establishment and reduce embryonic and fetal mortality following transfer of a cryopreserved in vitro-produced embryo., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The objective was to compare pregnancy per service event (P/S) in lactating dairy cows following timed artificial insemination (AI) or timed embryo transfer (ET) using either fresh or frozen in vitro-produced embryos. Oocytes were collected once per week for up to 9 wk using transvaginal ovum pick-up from elite dairy donors (ET-DAIRY; n = 40; Holstein-Friesian and Jersey) and elite beef donors (ET-ELITE-BEEF; n = 21; Angus). Both ET-DAIRY and ET-ELITE-BEEF donors consisted of heifers and cows. In addition, oocytes were collected from the ovaries of beef heifers of known pedigree following slaughter at a commercial abattoir (ET-COMM-BEEF; n = 119). Following in vitro maturation and fertilization, presumptive zygotes were cultured in vitro to the blastocyst stage. Grade 1 blastocysts were either transferred fresh or frozen for on-farm thawing and direct transfer. A total of 1,106 recipient cows (all lactating, predominantly Holstein-Friesian) located on 16 herdlets were blocked based on parity, calving date, and Economic Breeding Index, and randomly assigned to receive AI (n = 243) or ET (n = 863) after estrous synchronization with a 10-d Progesterone-synch protocol. Cows assigned to ET were further randomized to receive fresh (n = 187) or frozen (n = 178) ET-ELITE-BEEF embryos, fresh (n = 169) or frozen (n = 162) ET-DAIRY embryos, or fresh (n = 80) or frozen (n = 87) ET-COMM-BEEF embryos. Pregnancy was diagnosed using transrectal ultrasound on d 32 to 35 after synchronized ovulation and confirmed on d 62 to 65, at which time fetal sex was determined. Pregnancy per service event at d 32 was not different between AI (48.8%) and ET (48.9%) and did not differ between dairy and beef embryos (50.3% vs. 48.1%, respectively). However, P/S was less on d 32 following transfer of frozen embryos (41.6%) compared with fresh embryos (56.1%). Pregnancy loss between d 32 and 62 was greater for ET (15.1%) compared with AI (4.7%), with greater losses observed for frozen beef (18.5%), fresh beef (17.3%), and frozen dairy (19.2%) compared with fresh dairy (6.0%) embryos. Serum progesterone (P4) concentration on d 7 was associated with P/S at d 32 and 62. Cows in the quartile with the least serum P4 concentrations (quartile 1) had less probability of being pregnant on d 32 (33.4%) compared with cows in the 3 upper quartiles for serum P4 (45.7%, 55.6%, and 61.2% for quartile 2, quartile 3, and quartile 4, respectively). Sex ratio (male:female) at d 62 was skewed toward more male fetuses following ET (61.1:38.9) compared with AI (43.2:56.8) and was consistent with the sex ratio among in vitro blastocysts (61.2:38.8). In conclusion, P/S was similar for AI and ET, although pregnancy loss between d 32 and 62 was greater for ET than for AI., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The objective of this study was to characterize the species composition and functional potential of the vaginal and uterine microbiota at 1 wk postpartum in dairy cows diagnosed with or without purulent vaginal discharge (PVD) at 3 wk postpartum. The hypothesis was that differences in the vaginal and uterine microbiota between cows diagnosed with (PVD+) or without (PVD-) PVD were dependent on parity and breed. Cytobrush samples of the vagina and uterus were collected at 1 wk postpartum from 36 Holstein-Friesian (7 primiparous and 29 multiparous) and 29 Jersey (10 primiparous and 19 multiparous) cows. Microbial DNA was isolated from each sample and processed for shotgun metagenomic sequencing. The odds of multiparous cows being diagnosed as PVD+ was less compared with primiparous cows (OR = 0.21). Neither the α-diversity nor β-diversity of the uterine and vaginal microbiota were associated with PVD but the β-diversity was different between breeds and between parities. In the vagina of primiparous cows, differences in the microbiota of PVD- and PVD+ cows were minor, but the microbiota of multiparous PVD+ cows had greater relative abundance of Fusobacterium necrophorum, Trueperella pyogenes, Porphyromonas levii, and greater functional potential for amino acid and protein synthesis, energy metabolism, and growth compared with PVD- cows. The uterus of primiparous PVD+ cows had lesser relative abundance of Bacteroides heparinolyticus compared with PVD- cows. In the uterine microbiota, differences included greater functional potential for cellulose biosynthesis and fucose catabolism in multiparous PVD+ cows compared with PVD- cows. In the uterine microbiota of primiparous PVD+ cows, the functional potential for gram-negative cell wall synthesis and for negative regulation of tumor necrosis factor signaling was lesser compared with multiparous PVD+ cows. In the vagina of Holstein-Friesian PVD+ cows, the relative abundance of Caviibacter abscessus was greater whereas in the vagina of Jersey PVD+ cows the relative abundance of Catenibacterium mitsuokai, Finegoldia magna, Klebsiella variicola, and Streptococcus anginosus was greater compared with PVD- cows. In the uterine microbiota of Holstein-Friesian cows, the functional potential for spermidine biosynthesis was reduced compared with PVD- cows. In summary, differences in the species composition and functional potential of the vaginal and uterine microbiota between PVD- and PVD+ cows were dependent on parity and breed. The findings suggest that alternative strategies may be required to treat PVD for different parities and breeds of dairy cow., (© 2023, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The objective of this study was to evaluate the timing of artificial insemination (AI) with frozen-thawed sex-sorted semen on pregnancy per AI (P/AI) in dairy heifers. A 6-d progesterone Co-Synch protocol was used for ovulation synchronization of dairy heifers, with timed AI (TAI) coincident with (TAI-0) or 8 h (TAI-8) after the second injection of GnRH, corresponding to either 48 h or 56 h after removal of the progesterone-releasing intravaginal device. Pregnancy diagnosis was conducted by transrectal ultrasound scanning of the uterus 34 d after TAI (n = 816 records available for analysis). Generalized linear mixed models were used to examine the effects of treatment on P/AI. Treatment (n = 2), herd (n = 11), and treatment × herd were included as categorical fixed effects. Heifer body weight and Economic Breeding Index values for milk production, fertility, calving performance, beef carcass, cow maintenance, cow management, and health were included as continuous fixed effects. Heifer ID was included as a random effect. Pregnancy per AI was greater for TAI-8 heifers (59%) compared with TAI-0 heifers (50%). Pregnancy per AI ranged from 38% to 75% between herds but there was no treatment × herd interaction. The fertility subindex (positive) and the cow management subindex (negative) were the only continuous animal variables associated with P/AI. Delaying the timing of AI with frozen-thawed sex-sorted semen by 8 h in dairy heifers enrolled on a 6-d progesterone Co-Synch protocol improved P/AI., (© 2023.)

Within seasonal dairy systems, cows that calve late in the calving season are less likely to become pregnant and maintain a yearly calving interval. Very few studies have examined effective strategies for reproductive management of these late-calving cows. The objectives were to evaluate the reproductive performance of early- and late-calving dairy cows that were either inseminated after observed estrus (control) or enrolled in a timed AI and resynchronization protocol [progesterone (P4) Ovsynch Resynch)]. Early-calving cows calved during the first week of the calving season, whereas late-calving cows calved after 6 wk but were at least 10 d in milk at study commencement. Three dairy herds participated in the study with 391 cows total. Within each calving group, cows were randomly assigned to P4 Ovsynch Resynch or control (no treatment) in a 2 × 2 experimental design. Artificial insemination continued for 6 wk after mating start date (MSD) and was followed by 6 wk of natural service. The interval from MSD to AI was shorter (11.7 vs. 14.7 d) and the 3-wk pregnancy rate (49.5 vs. 21.2%) and the 6-wk pregnancy rate (60.8 vs. 42.4%) were greater in the early-calving compared with the late-calving control cows. By design, synchronized cows received timed AI on MSD and were not included in the statistical analysis of submission rate and interval from MSD to AI. The proportion of cows that received a second AI was not increased by the progesterone-based resynchronization strategy but was greater in early-calving compared with late-calving cows. The 12-wk pregnancy rate was greater (64.5 vs. 45.0%) in the early-calving synchronized cows compared with the late-calving synchronized cows. The interval from MSD to pregnancy was 6 and 12.6 d shorter for synchronized compared with control cows in the early- and late-calving groups, respectively. The results demonstrated reduced reproductive performance of late-calving cows compared with early-calving cows. Nonetheless, a major improvement to reproductive performance was achieved by targeting late-calving cows with a synchronization program, even when cows were only 20 to 50 DIM at first AI. Resynchronization of estrus with a progesterone device only, however, was not sufficient to increase the proportion of nonpregnant cows that received a second AI., (© 2021.)

Correctly identifying cows in estrus and inseminating them at the optimal time are critical components of reproductive management. Technologies for detecting cows in estrus have developed from tail paint in the 1970's to automated activity monitors and mount detectors in recent decades. The objectives of this study were to identify animal characteristics associated with estrous behaviour, measured using a mount detector (FlashMate; Farmshed Labs) and an accelerometer-based activity monitor (Moomonitor, Dairymaster), to examine the relationship between estrous behaviour measured by both devices, and to examine the characteristics associated with pregnancy per AI. Four hundred and sixty eight lactating dairy cows managed on three research farms were enrolled and data were available from 465 cows and 369 cows with Moomonitor and FlashMate data, respectively. Of 234 cows that provided both Moomonitor and FlashMate data, the mean (±SEM) onset of device activation occurred 1.1 (±0.4) h earlier with the Moomonitor compared with the FlashMate. The mean (±SD) duration of Moomonitor activity and FlashMate activity was 17.2 ± 6.1 h and 8.7 ± 5.8 h, respectively. The duration of Moomonitor activity and FlashMate activity was negatively associated with total milk yield during the first five weeks of lactation. The duration of FlashMate activity, but not the duration of Moomonitor activity was positively associated with days in milk. Pregnancy per AI was positively associated with BCS, days in milk, the duration of FlashMate activity and the interval from the onset of Moomonitor and FlashMate activity to AI. Inseminating cows ≤2 h after FlashMate activation or ≤4 h after Moomonitor activation was associated with reduced odds of pregnancy compared with later timing of AI. Overall, 55% of cows received mounts for ≤8 h, highlighting the need for ≥3 periods of estrous observation daily or the use of estrous detection aids that continuously monitor cows. Finally, the study reiterated the importance of maximising body condition score and days in milk at breeding to increase behavioural expression of estrus and pregnancy per AI., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The objective was to use ovulation synchronization with timed artificial insemination (TAI) to evaluate the effect of timing of artificial insemination (AI) with frozen sex-sorted sperm on fertility performance in pasture-based compact calving herds. Ejaculates from 3 Holstein-Friesian bulls were split and processed to provide frozen sex-sorted sperm (SS) at 4 × 10 6 sperm per straw, and frozen conventional sperm at 15 × 10 6 sperm per straw (CONV). A modified Progesterone-Ovsynch protocol was used for estrous synchronization, with TAI occurring 16 h after the second GnRH injection for cows assigned to CONV, and either 16 h (SS-16) or 22 h (SS-22) for cows assigned to SS. Pregnancy diagnosis was conducted by transrectal ultrasound scanning of the uterus 35 to 40 d after TAI (n = 2,175 records available for analysis). Generalized linear mixed models were used to examine the effects of treatment on pregnancy per artificial insemination (P/AI). Fixed effects included treatment (n = 3), bull (n = 3), treatment by bull interaction, parity (n = 4), days-in-milk category (n = 3), and treatment by days-in-milk category, with herd (n = 24) included as a random effect. Pregnancy per AI was greater for CONV compared with both SS-16 and SS-22 (61.1%, 49.0%, and 51.3%, respectively), and the SS treatments did not differ from each other (relative P/AI for SS-16 and SS-22 vs. CONV were 80.2% and 84.0%, respectively). There were significant bull and treatment by bull interaction effects. Additional analysis was undertaken using a model that included herd as a fixed effect. This analysis identified marked herd-to-herd variation (within-herd relative P/AI for the combined SS treatments vs. CONV ranged from 48-121%). The tertile of herds with the best performance achieved a mean relative P/AI of 100% (range = 91-121%), indicating that P/AI equivalent to CONV is achievable with SS. Conversely, the tertile of herds with the poorest performance achieved a mean relative P/AI of 67% (range = 48-77%). We found that SS resulted in poorer overall P/AI compared with CONV sperm regardless of timing of AI. Marked variation existed between herds; however, one-third of herds achieved P/AI results equal to CONV. Identification of factors responsible for the large herd-to-herd variation in P/AI with SS, and development of strategies to reduce this variation, warrant further research., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Uterine disease early postpartum reduces fertility during the breeding period. One potential mechanism involves the reduced functional capacity of the uterus to support pregnancy. A second potential mechanism involves damage to ovarian follicles associated with systemic inflammation. We categorized lactating Holstein cows into healthy (n = 63) and diseased (n = 39) uterus groups based on the percentage of polymorphonuclear neutrophils in the uterine lumen during the second and third month postpartum and evaluated the functionality of their ovaries and their capacity to establish and maintain pregnancy. Cows were enrolled in a timed artificial insemination protocol (Presynch Ovsynch) so that the first artificial insemination was approximately 75 d postpartum. Ovarian follicles and corpora lutea were counted and measured using transrectal ultrasound, ovulatory responses were assessed, and luteal phase progesterone concentrations were measured. Pregnancy was detected on d 18, 20, 22, 25, 32, and 45 through chemical (d 18 to 25) or ultrasonographic methods (d 32 and 45). The percentage of cows ovulating during the Presynch period; the number, diameter, and ovulatory capacity of follicles during the Ovsynch period; and plasma progesterone concentrations following ovulation were similar for healthy and diseased cows. The initial period of pregnancy establishment (d 18 to 22) appeared to be unaffected by disease because a similar percentage of healthy and diseased cows were pregnant during this period. Embryonic loss occurred in both healthy and diseased cows after d 22. Based on a relatively small number of pregnancies (n = 30 healthy and n = 17 diseased), the cumulative embryonic loss after d 22 was greater in diseased compared with healthy cows. In short, uterine disease as defined in this study did not affect cyclicity, ovarian follicular growth, or plasma progesterone concentrations. Percentages of healthy and diseased cows that were pregnant were similar from d 18 to 22 after artificial insemination. Greater embryonic loss was observed after d 22 in diseased compared with healthy cows, but this observation was based on a small number of pregnancies and should be studied further in larger trials with greater statistical power., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Less than optimal circulating progesterone as well as glucose, insulin, and IGF1 concentrations in lactating cows may contribute to embryonic loss if placental development is dependent on concentrations of these hormones. There was comparison of fetal growth in lactating dairy cows with a contemporary group of nulliparous heifers (negative control for lactation). There was also assessment of the association between conceptus development and circulating hormone and metabolite concentrations and the response to an intravenous glucose administration. The embryo and amniotic vesicle were measured every 2-3 days during a 2-week period (days 33-45 of pregnancy). Blood samples were collected at the time of ultrasonography and analyzed for glucose, insulin, IGF1, and progesterone. There was also an intravenous glucose administration. Lactating cows had lesser blood concentrations of glucose, progesterone, and IGF1 during pregnancy. With respect to glucose administration, cows had lesser insulin and glucose than heifers at time 0 but heifers released three-fold more insulin than cows in response to glucose infusion. Cows had slightly larger fetuses when compared with heifers. When included in the model for embryo or amniotic vesicle length or area, concentrations of circulating glucose, insulin, IGF1, or progesterone did not explain a large amount of variation in values for these variables (P > 0.10). The conclusion was that cows differed from heifers for fetal growth but concentrations of circulating metabolites were not associated with size of the fetus. There was no evidence for an association between the hormonal or metabolic milieu and conceptus development., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

The hypothesis of this study was that cows with good genetic merit for fertility traits (Fert+) would produce oocytes and embryos of greater quality than cows with poor genetic merit for fertility traits (Fert-) and that mRNA expression of candidate genes would reflect the observed differences in quality. The aim of the study, therefore, was to determine the effect of genetic merit for fertility traits on morphological classification and mRNA abundance of key genes in immature oocytes and cumulus cells following ovum pick-up and in embryos following superovulation, artificial insemination (AI), and uterine flushing. In experiment 1, 17 Fert+ and 11 Fert- cows, ranging from 54 to 84 d in milk, were submitted to ovum pick-up on 4 occasions during a 2-wk period. Recovered cumulus-oocyte complexes (COC) were morphologically graded. Oocytes and cumulus cells were separated, and mRNA abundance of genes associated with oocyte developmental competence was measured. There was no effect of genotype on the distribution of COC grades or on the mRNA abundance of the candidate genes in grade 1 COC. In experiment 2, 20 Fert+ and 19 Fert- cows, ranging from 71 to 189 d in milk, were submitted to superovulation and AI. The uteri of cows that responded to the superovulation protocol (17 Fert+ and 16 Fert- cows) were nonsurgically flushed 7 d postovulation. Recovered embryos were morphologically graded, and mRNA abundance of genes associated with embryo development was measured in grade 1 blastocysts. The response to the superovulation protocol was assessed by counting the number of codominant follicles on the day of AI, which was similar for both genotypes (22.0 ± 9.7 and 19.8 ± 8.2 for Fert+ and Fert- cows, respectively). There was no effect of genotype on the proportion of transferable embryos recovered or on the mRNA abundance of the candidate genes tested in the grade 1 blastocysts. Of the total embryos classified as blastocysts, however, the Fert+ cows tended to have a greater proportion of grade 1 blastocysts compared with Fert- cows (90% vs. 64%, respectively). In conclusion, genetic merit for fertility traits had a no effect on mRNA abundance of the candidate genes that were examined in immature oocytes and cumulus cells and in embryos recovered after superovulation. The observed differences in morphological blastocyst quality following superovulation would suggest that the superior reproductive performance of Fert+ cows could arise during the later stages of embryo development from d 7 until maternal recognition of pregnancy., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Fatty liver is a common condition affecting dairy cattle during the periparturient period, characterized by a pathological accumulation of triglycerides (TG) in the hepatocytes. The objective of this study was to evaluate the diagnostic potential of fine needle aspiration cytology in fresh liver specimens using liver TG concentrations as a gold standard. Fifty-seven liver samples from Holstein cows were collected during processing at a slaughterhouse. Tissue and fine needle aspirate samples were obtained from the parietal upper portion of the caudate lobe. Two samples of liver tissue were collected with a 16 gauge × 15 cm biopsy needle for histological and TG concentration assessment. A third sample was collected for cytology using an 18 gauge × 5.08 cm needle. The contents of the needle were transferred to a glass slide, spread, and air-dried. Liver samples were assayed by colorimetry/fluorimetry to determine TG concentrations. Concentrations of TG <2% were considered normal. Histological and cytological evaluations were conducted by 2 different pathologists blind to the visual classification. Sensitivity (Se) and specificity (Sp) were calculated. Cytology had a Se and Sp of 73 and 85%, respectively. Histopathology had a Se and Sp of 45.9 and 100%, respectively. The likelihood of having higher scores for histopathology and cytology increased as a function of liver TG content (mg/g)., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

A hypothetical explanation for pregnancy loss in postpartum dairy cows is that the metabolic environment of the cow inhibits the growth of the conceptus and places the pregnancy at risk for loss. The objective of the current study, therefore, was to model the association between cow-level metabolic indicators and conceptus growth during early pregnancy (day 33-45 after AI) and to determine if an association (if present) is large enough to cause pregnancy loss. Metabolic indicators included milk production, changes in body weight and body condition score, parity, and concentrations of circulating hormones and metabolites (glucose, non-esterified fatty acids, growth hormone, IGF1, progesterone, and pregnancy-associated glycoproteins). One-hundred cows were enrolled. Cows that became pregnant with single conceptus pregnancies (n=53) weighed more (P<0.007) and had fewer uterine polymorphonuclear neutrophils (uterine health indicator; P<0.051) compared with cows that failed to become pregnant. The embryo and amniotic vesicle were measured by using ultrasound on day 33, 35, 38, 40, 42, and 45 of pregnancy. Most of the cow-level indicators that were included in the model of conceptus growth failed to achieve statistical significance. Day of pregnancy had the largest effect on conceptus growth (size and cross-sectional area of the embryo and amniotic vesicle; P<0.001). There were effects of sex of fetus (male fetuses larger than female), insulin (negative association), and body weigh change (positive association) on embryo length and cross-sectional area but these effects were small when compared with the range in conceptus length or area that we observed. The conclusion was that the capacity of the cow to become pregnant was associated with body weight and uterine health but we failed to find a large association with metabolic status on conceptus growth from day 33 to 45 of pregnancy in lactating dairy cows., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: CYP2D6 is a critical enzyme in the metabolism of tamoxifen and potentially a key determinant in breast cancer outcomes. Our study examined patients' beliefs about how the CYP2D6 genotype would affect their prognoses., Methods: Women enrolled in a pharmacogenomic clinical trial and on tamoxifen for prevention or treatment of breast cancer underwent CYP2D6 genotyping (EM = extensive, IM = intermediate, PM = poor metabolizing alleles). The informed consent said that the purpose of the trial was to examine effects of dose adjustment based on genotype, but that clinical benefits were uncertain. Our embedded sub-study surveyed 320 patients prior to receiving their genotypes. We experimentally manipulated 6 vignettes to describe hypothetical tamoxifen treatment (no or yes) and hypothetical genotype (EM, IM or PM). For each vignette, women gave their perceived recurrence risk (RR; 0-100%)., Results: Women believed that genotype would not affect their RR if they did not take tamoxifen (p = 0.06). However, women believed that if prescribed tamoxifen, genotype would affect their RR (22% if EM, 30% if IM and 40% if PM, p < 0.001)., Conclusion: Women believed that extensive tamoxifen metabolizers had better prognoses, despite study materials stating uncertainty about any benefit. The rapidly changing nature of genomic science calls for caution when communicating clinical utility.

Following the introduction 30 years ago of neonatal screening and early dietary treatment for phenylketonuria there has been a dramatic decrease in the severity of neurological dysfunction associated with this disorder. However, there is evidence that subtle neurological impairment remains common in early treated subjects and in the last 3 years there have been a number of reports of overt neurological impairment with white matter abnormalities on MRI. The frequency of white matter changes in phenylketonuria, and the relation of these changes to dietary management, have remained unclear. The present study examines MRI findings in 34 subjects aged 8-33 years. Twenty-five subjects had been detected by routine neonatal screening and nine had been missed in the screening programme. At the time of the investigation 16 of the early treated and two of the late treated subjects were still receiving a diet low in phenylalanine. All but two of the 34 subjects showed abnormalities on MRI. In the early diagnosed group it could be shown that the severity of MRI changes (graded 1-5) was significantly and independently associated with phenylalanine concentrations at the time of investigation and the time since dietary treatment had been withdrawn. These data are consistent with studies in animals showing that hyperphenylalaninaemia increases myelin turnover in a dose dependent manner. It is suggested that the effects of phenylalanine on myelin pose a lifelong hazard to the nervous system.

A description of the establishment, operation, and programmatic foci of the Center for Early Education and Development (CEED) is provided. CEED offers a model for creating links between the research resources of a University and professionals who work directly with young children and families. CEED's role in demystifying research and making it accessible for community practitioners is an important one in bridging the gap between the trenches and the ivory tower.

A case of tuberous sclerosis in a neonate, with cerebral and cardiac hamartomas evaluated by MR imaging, is presented. Intracranial subependymal tubers in this neonate exhibit increased signal intensity on short TR images. This differs from the signal characteristics of subependymal tubers in older patients.

Knowledge of the chronologic evolution of bone-marrow changes during and after radiation therapy is essential in differentiating normal postradiation changes from other marrow abnormalities. The appearance of the lumbar vertebral bone marrow was studied on 55 serial spin-echo and short-T1 inversion-recovery (STIR) MR images obtained in 14 patients receiving radiation therapy for Hodgkin disease, seminoma, or prostate carcinoma. Images were obtained before, at weekly intervals during, and at various monthly intervals up to 14 months after a 3- to 6-week course of fractionated paravertebral lymph-node irradiation of 1500-5000 rad (15-50 Gy). During the first 2 weeks of therapy, there was no definite change in the appearance of the marrow on spin-echo images; however, there was an increase in signal intensity on the STIR images, apparently reflecting early marrow edema and necrosis. Between weeks 3 and 6, the marrow showed an increasingly heterogenous signal and prominence of the signal from central marrow fat, shown best on T1-weighted images. Late marrow patterns (6 weeks to 14 months after therapy) varied and consisted of either homogenous fatty replacement or a band pattern of peripheral intermediate signal intensity, possibly representing hematopoietic marrow surrounding the central marrow fat. No focal marrow lesions or soft-tissue edema were identified during the course of radiation therapy; their presence should raise the possibility of the presence of a pathologic process other than radiation change. These data suggest that MR can detect radiation-induced marrow changes as early as 2 weeks after starting therapy, and that there are at least two distinct types of late marrow MR patterns.

T1-weighted magnetic resonance (MR) images of the femur in 77 subjects, aged 1 month to 24 years, were retrospectively analyzed for the distribution and appearance of red and yellow marrow. The subjects were divided into six age groups, and the signal intensity and degree of mottling of marrow in the proximal epiphysis, proximal metaphysis, diaphysis, distal metaphysis, and distal epiphysis were observed and assigned a grade. Bone marrow with low or intermediate to slightly increased signal intensity was considered red marrow, while bone marrow with increased signal intensity was considered fatty marrow. An orderly progression of red to yellow marrow conversion in the femur was appreciated first in the diaphysis (ages 1-10 years) and then in the distal metaphysis (ages 10-20 years), with an adult pattern seen by age 24 years. The MR spectrum of red and yellow marrow differs from the existing macroscopic anatomical data because MR imaging is apparently more sensitive to the presence of microscopic fat in bone marrow.

The relative efficacies of cranial magnetic resonance imaging (MRI) and computed tomography (CT) brain scans for the detection of intracranial pathology in patients with the acquired immune deficiency syndrome (AIDS) were evaluated prospectively. Fifty homosexual or bisexual men with AIDS and neurologic symptoms were evaluated using both modalities. In 24 patients, MR images and CT scans provided the same diagnostic information (within normal limits in 16, cerebral atrophy only in 6, and similar lesions in 2 patients). In only one instance did CT show the presence of a lesion not seen on MRI. In the 25 remaining patients, MRI was the more sensitive modality. MRI also reflected more consistently the histopathologically documented extent and distribution of central nervous system disease. The greater sensitivity of MRI suggested significant alterations in the diagnostic evaluation and therapeutic management of 20 patients. Thus, MRI was as good or better than CT for the detection of intracranial pathology in 49 of 50 neurologically symptomatic AIDS patients and significantly affected the diagnosis and treatment of 40% of these patients. Although MRI does not appear to be more specific than other modalities in the differentiation of human immunodeficiency virus (HIV)-related neurologic diseases, its greater sensitivity suggests that MRI may be the best neuroimaging procedure for the initial radiologic evaluation of AIDS patients with neurologic illness.

Escherichia coli that are lysogenic for a lambda-lacZ fusion phage produce beta-galactosidase, product of the lacZ gene, upon induction of the prophage by DNA-damaging agents. The miniaturization of a quantitative, colorimetric beta-galactosidase (prophage) induction assay (BIA) is presented. Induction assays are performed in microtiter wells with the aid of multichannel pipetting devices. Results are shown with screening strain BR513 (uvrB delta envA) and a strain, BR339 (uvrB delta lexA3ind-) which exhibits enhanced induction. A method developed for strain BR339 utilizes bacteria stored frozen in log phase, permeabilized in vitro, and used immediately; with this method, 2 consecutive assays may be completed in 1 working day. Mutagens utilized for the model studies included 4NQO, ENNG, daunorubicin, bleomycin, acetoxy-AAF, B[a]P, DMBA, and DEN (the last three in the presence of liver S9). Induced levels of beta-galactosidase were monitored using a vertical light path photometer that measured color absorbance in each microtiter well. Alternatively, color intensity could be determined by using a color chart prepared for this assay. These values were then plotted to generate dose-response curves. Considerable savings in labor and materials are achieved with the method described, one which may be used as a screen for DNA-damaging chemicals. Automated equipment and computers may be used to advantage with this assay, but they are not required.

As part of our effort to validate a biochemical (prophage) induction assay (BIA) as a screening test for carcinogens, we have tested more than 100 N-nitroso compounds. An enzyme, beta-galactosidase, is induced as an indirect consequence of DNA damage to the host, as part of the 'SOS' response. Besides the obvious practical importance of detecting this class of carcinogen, there is the question of the mechanism by which these compounds work. Mutagenesis by one compound, N-methyl-N'-nitro-N-nitrosoguanidine, is known to proceed by both SOS (recA)-dependent and SOS-independent pathways. Mispairing due to O6 alkylation of guanine is thought to be responsible for the SOS-independent pathway; however, there has been little consideration of recA-dependent functions, of which phage induction is one. Although nitrosamides could be detected as phage inducers in our assay, N-nitrosamines in the presence of rat liver 9 000 X g supernatant usually gave no response. We found that the use of several mutant strains, particularly a lexA mutant, in combination with hamster liver 9 000 X g supernatant, allowed us to detect most N-nitrosamines reasonably well, in either a spot test or a quantitative tube assay. Induction in a lexA strain was most unexpected, since this mutation usually diminishes the expression of SOS functions induced by ultra-violet light. Because the genetic and biochemical conditions that favour phage induction are different from those that favour mutagenesis, it seems likely that the lesions in DNA leading to the two biological end-points are different.

Magnetic resonance imaging of the musculoskeletal system in general and the hip in particular offers many exciting opportunities for innovative and revolutionary diagnostic avenues, the full potential of which awaits further investigative and clinical experience.

The role of MR in evaluating tuberous sclerosis is reviewed in 15 patients. These studies were compared with CT scans, which were available in 14 patients. Four characteristic findings were noted on the MR images obtained. Subependymal nodules projecting into the lateral ventricles were seen in 12 of 15 patients on T1-weighted images. This was the most specific finding. Distortion of the normal cortical architecture was seen in 10 of 11 patients in whom T1-weighted images were obtained using a 256 X 256 matrix. These foci corresponded to multiple cortical areas of increased signal on T2-weighted images. Dilated ventricles were seen in five patients. In one patient, a known astrocytoma showed increased signal on the T2-weighted images, allowing differentiation from a benign subependymal nodule. MR depicted the cortical hamartomas more completely than did CT. The MR scans were abnormal in all cases, and a diagnosis could be confidently made in all 11 cases scanned using a 256 X 256 matrix. Our preliminary experience suggests that MR will at least equal and probably exceed CT, both for sensitivity and specificity, given the use of a 256 X 256 matrix.