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The present study compared 2 strategies to initiate a progesterone (P4)-based timed artificial insemination (TAI) protocol for lactating dairy cows: only GnRH or estradiol benzoate (EB) plus GnRH (EB+GnRH). Lactating Holstein cows (n = 487; 184 primiparous and 303 multiparous) from 2 commercial dairy herds were used for their second or greater services postpartum. Each week, cows that were nonpregnant at the pregnancy diagnosis 32 d after a previous AI were randomly assigned to 1 of 2 experimental groups that differed only in the strategy to initiate (d 0) the TAI protocol. On d 0, every cow received a 2.0-g P4 implant; in the EB+GnRH group, cows were treated with 2.0 mg i.m. of EB and 16.8 µg i.m. of the GnRH analog buserelin acetate, whereas in the GnRH group, cows received only 16.8 µg i.m. of GnRH. On d 7 after the initial treatment, 0.530 mg i.m. of cloprostenol sodium (PGF) was administered in all cows, followed by a second dose on d 8, concomitant with 1.0 mg i.m. of estradiol cypionate and P4 implant withdrawal. The TAI was performed on d 10 (48 h after P4 device withdrawal) in both experimental groups. Only conventional Holstein semen was used throughout the study. The percentage of cows with corpus luteum (CL) on d 0 (73%) and overall ovulation rate after d 0 (54%) did not differ between groups. The CL regression between d 0 and the first PGF treatment was greater in the EB+GnRH group than the GnRH group (42% vs. 31%). Consequently, the proportion of cows with CL at PGF was greater when only GnRH was used on d 0 compared with EB+GnRH (86% vs. 82%), and the mean number of CL at PGF was greater (1.23 vs. 1.11). The expression of estrus near TAI was greater in GnRH group (84% vs. 77%), and cows showing estrus had greater (44% vs. 10%) pregnancy per AI (P/AI) on d 32 for both treatments. We found no effect of the presence of CL on d 0 or at PGF, nor of ovulation after d 0 or CL regression between d 0 and d 7 on fertility. However, fertility was critically impaired when cows did not have CL at both times, d 0 and at PGF treatment. We did not observe any interaction between treatment and other variables, and the P/AI was similar in cows receiving EB+GnRH or only GnRH on d 0 (37.8% vs. 36.6%). In summary, although there was no detectable difference in P/AI between treatments, this study demonstrated potential negative physiological outcomes caused by EB treatment on d 0 (greater incidence of luteolysis after d 0 and fewer cows with CL at PGF treatment). Overall, we found no benefit of adding EB at the initiation of a P4-based TAI protocol on fertility compared with using GnRH alone, despite differences in ovarian dynamics and expression of estrus., (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/).)

This study evaluated the influence of GnRH analogs (gonadorelin vs. buserelin) and doses (single vs. double) on LH release and ovulatory response in Bos indicus (Nelore) females on Day 7 of the estrous cycle. Cycling heifers and non-lactating cows were pre-synchronized: Day -10: progesterone (P4) implant insertion plus 2 mg of estradiol benzoate; Day -2: implant removal and 0.53 mg of cloprostenol sodium (PGF); Day 0: 25 μg of lecirelin (GnRH). Over four replicates, heifers (n = 57) and cows (n = 53) that ovulated to the GnRH treatment on Day 0, having a visible corpus luteum (CL) and a dominant follicle (DF) ≥ 8.5 mm, were allocated to receive the following GnRH treatments on Day 7: G-Single (100 μg of gonadorelin); G-Double (200 μg of gonadorelin); B-Single (10 μg of buserelin); and B-Double (20 μg of buserelin). At GnRH treatment, a P4 implant was inserted in heifers (0.5 g) and cows (1 g). Ultrasound examinations were done on Days -10, -2, 0, 2, 7, 9, 12, and 14 to evaluate DF diameter, ovulation and presence of CL. Blood samples were collected on Day 7 at 0, 2, and 4 h from GnRH treatment, to evaluate circulating P4 and LH concentrations. On Day 12, the P4 implant was removed, females received two PGF treatments (24 h apart), and 2 d later, 25 μg of GnRH was given to start the next replicate. In both heifers and cows, P4 concentrations were elevated on Day 7, and similar among groups (3.9 and 4.2 ng/mL, respectively). In heifers, buserelin induced greater LH peak (9.5 vs. 2.6 ng/mL; P < 0.01) and greater ovulation (88.9 [24/27] vs. 16.7% [5/30]; P < 0.01) than gonadorelin treatments, regardless of the dose. Similarly, in cows, buserelin induced greater LH peak than gonadorelin (9.9 vs. 4.9 ng/mL; P < 0.01). However, ovulation was only increased in cows from the B-Double group (90.9% [10/11]), whereas in the other groups the ovulatory response was similar (35.7% [15/42]). Regardless of treatment, heifers had similar P4 concentrations (P = 0.22), but smaller DF (P < 0.01) than cows on Day 7. Only in G-Double group the LH peak was lower (P = 0.05) in heifers than in cows, with no difference within other groups. In heifers, but not in cows, the single dose of buserelin resulted in high ovulatory response, equivalent to that produced by the double dose. In conclusion, in Bos indicus heifers and cows on Day 7 of the cycle, with elevated P4 concentrations, buserelin induced greater LH release and ovulatory response than gonadorelin treatments. Double doses increased the LH release, however, only resulted in greater ovulation in females treated with buserelin. Finally, although circulating P4 concentrations did not differ between parities, heifers were more likely to ovulate in response to a GnRH-induced LH peak than cows., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The objective of the present study was to evaluate effects of synchronization of timing of follicle wave emergence, before ovarian superstimulation and ovum pick-up (OPU), on ovarian response and embryo production in pregnant heifers. Pregnant (47-69 days of gestation) Holstein heifers (n = 64), 19.0 ± 0.3 months of age, were assigned in a completely randomized design to one of two groups: synchronization of follicular wave emergence using follicle ablation (Synchronized) or untreated control (Non-synchronized). Superstimulatory treatments consisting of 160 mg (280 IU) of porcine follicle stimulating hormone (p-FSH), administered in four decreasing dose treatments 12 h apart, were initiated 36 h after follicle ablation or at random stages of the follicular wave in heifers of the Synchronized and Non-synchronized group, respectively. Ovum pick-up was performed in all heifers 40 h after the last p-FSH administration and retrieved cumulus oocyte complexes (COCs) were subjected to in vitro embryo production (IVEP) procedures. Ultrasonography was performed immediately before OPU to determine number and size of ovarian follicles. Differences in treatment responses between groups were evaluated using generalized linear mixed models. Total number of follicles at the time of OPU was not different between treatment groups (P = 0.61), however, the number of small follicles (<6 mm) was greater (P = 0.05) in heifers of the Non-synchronized group, whereas number of medium size follicles (6-10 mm) tended (P = 0.09) to be greater in heifers of the Synchronized group. Heifers in the Synchronized group had a greater (P = 0.01) percentage of medium sized follicles and a lesser (P = 0.01) percentage of smaller sized follicles than heifers in the Non-synchronized group. There were no differences (P > 0.15) in total number of recovered COCs, or number of viable COCs between groups. Cleavage percentage (84.5% and 72.8%) and blastocyst percentage (48.2% and 33.4%) were greater (P < 0.01) in heifers of the Synchronized than Non-synchronized group, respectively. As a result, mean number of blastocysts per OPU/heifer was greater (P = 0.006) in the heifers of the Synchronized (8.9 ± 1.0) than the Non-synchronized (5.5 ± 0.9) group. In conclusion, synchronizing the time of follicle wave emergence in pregnant heifers, prior to ovarian superstimulation with FSH and OPU results in a greater superstimulatory response and oocyte competence leading to greater embryo production., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Inappropriate corpus luteum (CL) regression can produce pregnancy loss. An experimental model was utilized to investigate regression of accessory CL during pregnancy in dairy cows. Cows were bred (day 0) and treated with gonadotrophin-releasing hormone 6 days later to form accessory CL. Transrectal ultrasound (every other days) and blood samples for progesterone (P4; daily) were performed until day 56 of pregnancy. On day 28, 13 cows were confirmed pregnant, and accessory CL were found contralateral (n = 9) or ipsilateral (n = 4) to previous ovulation. On day 18, CL biopsy was performed to analyze mRNA expression for interferon-stimulated genes (ISGs). Luteolysis occurred more frequently in cows that had contralateral accessory CL (88.9% (8/9)) than in cows with ipsilateral accessory CL (0% (0/4)). Luteolysis of contralateral accessory CL occurred either earlier (days 19-23; 2/8) or later (days 48-53; 6/8) in pregnancy and occurred rapidly (24 h), based on daily P4. After onset of earlier or later accessory CL regression, circulating P4 decreased by 41.2%. There was no difference in luteal tissue mRNA expression for ISGs on day 18 between accessory and original CL and between CL that subsequently regressed or did not regress. On day 56, an oxytocin challenge dramatically increased prostaglandin F2α metabolite (PGFM) in all cows but produced no pregnancy losses, although cows with previous accessory CL regression had greater PGFM. In summary, ipsilateral accessory CL did not regress during pregnancy, whereas most contralateral CL regressed by 63 days of pregnancy, providing evidence for local mechanisms in regression of accessory CL and protection of CL during pregnancy.

Objective: The most important indication for EEGs is the investigation of epileptic and nonepileptic seizures. However, it is unclear whether EEG in the emergency depatment (ED) can be useful in managing other conditions. Our objective was to investigate the usefulness of EEGs in the ED., Methods: We performed an observational, descriptive, retrospective study based on clinical records between 2018 and 2019. We evaluated patients admitted to our ED or hospital wards who underwent an EEG. We defined the EEG results as useful when they prompted changes in antiepileptic drug (AED) treatment or clinical management., Results: We gathered information from 236 patients with a mean age of 59.23 years (SD ±22.6), of whom 47.9% were women. In patients with seizures, 18.2% were generalized, 27.1% were focal, and 18.6% were unknown. Overall, 25.8% of the EEGs were abnormal. However, in patients with a history of predisposing conditions for epileptic seizures or encephalopathies, the tracing was abnormal in 47.5%. The most frequent alteration on the abnormal EEGs was generalized slowing (18.2%). The EEG was useful in 76.7% of patients: AEDs changed in 8.4% and clinical management changed in 76.2% of patients. The usefulness of EEGs associated with acute ischemic lesions on CT ( p = 0.023) and with the diagnosis of vasovagal syncope ( p = 0.022)., Conclusions: Routine EEG is useful in the ED, even in patients with a normal CT or MR brain image, because it helps determine clinical management or AED changes., (© 2021 American Academy of Neurology.)

Changes in circulating progesterone (P4) and estradiol (E2) during proestrus produce dynamic changes in endometrial function and pituitary release of gonadotropins. Independent and combined effects of P4 and E2 on endometrium and pituitary were evaluated. In a preliminary study, an exogenous hormone model of proestrus was created by removal of corpus luteum and follicles ≥5 mm followed by gradual removal of intravaginal P4 implants during 18 h and treatment with increasing doses of estradiol benzoate during 48 h to mimic proestrus using high E2 (n = 9) or low E2 (n = 9). Decreased P4, increased E2, and increased endometrial area (EA) simulated proestrus in high-E2 cows and this was used subsequently. The main experiment used a 2 × 2 factorial design with: high E2 and low P4 (n = 11); high E2 and high P4 (n = 11); low E2 and high P4 (n = 11); low E2 and low P4 (n = 10). At 48 h, gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) and follicle stimulating hormone (FSH) release was determined. Variables were analyzed using PROCMIXED of Statistical Analysis System. The EA increased dramatically during 48 h only in high-E2 and low-P4 cows. For FSH, high-E2 cows had greater area under the curve (AUC) and FSH peak after GnRH than low E2, with mild negative effects of high P4. For LH, concentration at peak and AUC were 2-fold greater in high E2 compared to low-E2 groups, with low P4 also 2-fold greater than high-P4 groups. Thus, maximal changes in uterus and pituitary during proestrus depend on both low P4 and high E2, but different physiologic responses are regulated differently by E2 and P4. Changes in endometrium depend on low P4 and high E2, whereas GnRH-induced FSH secretion primarily depends on high E2, and GnRH-induced LH secretion is independently increased by high E2 or reduced by high P4., (© The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The objective of this study was to compare the clinical and immunological presentation of SLE between males and females in a Colombian SLE population. A cross-sectional, retrospective study was performed that evaluated patients with SLE over 6 years. The dependent variables were systemic complications, duration of hospitalization, readmission, and death. Descriptive, group comparison, bivariate, and multivariate analysis were performed using Stata 12.0 software 200 patients were included in this study, 84.5% were females and 15.5% males. Longer hospitalizations, readmissions, respiratory compromise, higher activity disease (ECLAM score), smoking, and use of cyclophosphamide in the past 3 months were more prevalent in males. In the bivariate and multivariate analysis, we found an increased risk in males of respiratory symptoms (OR 3.35), anti-DNA antibody (OR 2.46), smoking (OR 4.2), cyclophosphamide use (OR 3.23), chronic pulmonary alterations (OR 2.51), readmission (OR 2.88), long hospitalization (OR 3.12), and death (OR: 3.31). This is the first study that shows the differences related to gender in Colombian SLE patients. Males with SLE have more disease activity compare with females. Also, we found that males have more risk of pulmonary impairment, longer hospitalizations, hospital readmissions, and deaths.

The number of species of anurans in the Amazon is highly underestimated with new studies reporting the discovery of a large number of species every year. This advance in the discovery of biodiversity is due to the use of molecular tools, especially 16S rRNA gene barcoding, which is used to identify species and discover cryptic lineages. Few anurans of the central Amazon have molecular sequence data available in public databases, which contrasts with the considerable species richness of this biome. The aim of the present study was to test for the presence of cryptic species using the mPTP delimitation algorism. We morphologically identified 26 species, of which 23 were confirmed molecularly with the remaining three species identified as other congeneric species, since sequences with the same epithet do not exist in GenBank. Of these 23 species, nine contained one lineage restricted to central Amazon. This represents an underestimate of 39% in the taxonomic diversity in our sample. This is particularly surprising given that our sampling sites are among the best-studied regions of the central Amazon.

In ruminants, uterine pulses of prostaglandin (PG) F2α characterize luteolysis, while increased PGE2/PGE1 distinguish early pregnancy. This study evaluated intrauterine (IU) infusions of PGF2α and PGE1 pulses on corpus luteum (CL) function and gene expression. Cows on day 10 of estrous cycle received 4 IU infusions (every 6 h; n = 5/treatment) of saline, PGE1 (2 mg PGE1), PGF2α (0.25 mg PGF2α), or PGE1 + PGF2α. A luteal biopsy was collected at 30 min after third infusion for determination of gene expression by RNA-Seq. As expected, IU pulses of PGF2α decreased (P < 0.01) P4 luteal volume. However, there were no differences in circulating P4 or luteal volume between saline, PGE1, and PGE1 + PGF2α, indicating inhibition of PGF2α-induced luteolysis by IU pulses of PGE1. After third pulse of PGF2α, luteal expression of 955 genes were altered (false discovery rate [FDR] < 0.01), representing both typical and novel luteolytic transcriptomic changes. Surprisingly, after third pulse of PGE1 or PGE1 + PGF2α, there were no significant changes in luteal gene expression (FDR > 0.10) compared to saline cows. Increased circulating concentrations of the metabolite of PGF2α (PGFM; after PGF2α and PGE1 + PGF2α) and the metabolite PGE (PGEM; after PGE1 and PGE1 + PGF2α) demonstrated that PGF2α and PGE1 are entering bloodstream after IU infusions. Thus, IU pulses of PGF2α and PGE1 allow determination of changes in luteal gene expression that could be relevant to understanding luteolysis and pregnancy. Unexpectedly, by third pulse of PGE1, there is complete blockade of either PGF2α transport to the CL or PGF2α action by PGE1 resulting in complete inhibition of transcriptomic changes following IU PGF2α pulses.

Background: Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS)., Methods: Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations., Results: 5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively. In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS., Conclusion: Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA.