Selective serotonin reuptake inhibitors (SSRIs) have been linked to osteopenia and fracture risk; however, their long-term impact on bone health is not well understood. SSRIs are widely prescribed to pregnant and breastfeeding women who might be at particular risk of bone pathology because lactation is associated with considerable maternal bone loss. We used microCT and molecular approaches to test whether the SSRI fluoxetine, administered to C57BL/6 mice from conception through the end of lactation, causes persistent maternal bone loss. We found that peripartum fluoxetine increases serum calcium and reduces circulating markers of bone formation during lactation but does not affect osteoclastic resorption. Peripartum fluoxetine exposure also enhances mammary gland endocrine function during lactation by increasing synthesis of serotonin and PTHrP, a hormone that liberates calcium for milk synthesis and reduces bone mineral volume. Peripartum fluoxetine exposure reduces the trabecular bone volume fraction at 3 months after weaning. These findings raise new questions about the long-term consequences of peripartum SSRI use on maternal health.

Our objective was to assess the effect of treatment with human chorionic gonadotropin (hCG) 7 d after artificial insemination (AI) or at the time of in vitro-fertilized (IVF) embryo transfer on reproductive outcomes, including progesterone (P4), interferon-tau stimulated gene 15 (ISG15), pregnancy-specific protein B (PSPB), and pregnancies per AI (P/AI) or pregnancies per embryo transfer (P/ET), in nulliparous Holstein heifers. Heifers in experiment 1 were randomly assigned to receive no treatment (control; n = 129) or 2,000 IU of hCG 7 d after AI to a detected estrus (estrus = experimental d 0; hCG; n = 132). Heifers in experiment 2 were randomly assigned to receive no treatment (control; n = 143) or 2,000 IU of hCG (hCG; n = 148) at transfer of an IVF embryo 7 d after the last GnRH treatment of a 5-d controlled internal drug release-synch protocol (last GnRH = experimental d 0). Blood samples were collected from a subgroup of heifers (experiment 1, n = 82; experiment 2, n = 104) at d 7, 11, 18, 20, 25, 28, and 32, and blood samples from heifers diagnosed pregnant were collected on d 35, 39, 46, 53, 60, and 67. Blood samples were assayed for P4 by RIA and for PSPB by ELISA, and expression of ISG15 was assessed in mRNA isolated from blood leukocytes on d 18 and 20. Data were analyzed by ANOVA and logistic regression using the MIXED and GLIMMIX procedures. In both experiments, treatment with hCG increased P4 concentrations from d 11 to 32; however, treatment did not affect P/AI or P/ET at d 32 or 67, PSPB concentrations from d 11 to 67 of pregnancy, or relative ISG15 mRNA concentrations on d 18 or 20. Heifers diagnosed not pregnant at d 32 in experiment 2 with an extended luteal phase (>20 d) and treated with hCG had greater relative ISG15 mRNA concentrations on d 20 than control heifers. Treatment with hCG did not affect pregnancy loss in experiment 1, whereas heifers treated with hCG at the time of IVF embryo transfer had fewer pregnancy losses from d 32 to 67 than control heifers. We concluded that treatment with 2,000 IU of hCG 7 d after AI or at the time of embryo transfer increased P4 concentrations without affecting P/AI or P/ET in nulliparous Holstein heifers.

The onset of lactation requires a variety of physiological adaptions as a mammal transitions from a non-lactating to lactating state. In order to initiate lactation, a coordination of changes in tissue metabolism occurs in response to the physiological demands of lactation. Due to these immense nutrient demands by the mammary gland, many maternal adaptations occur to support lactation (Bauman & Currie, 1980). To meet these demands, in addition to traditionally

Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressant used by pregnant women; however, they have been associated with adverse pregnancy outcomes and perinatal morbidity in pregnant women and animal models. We investigated the effects of two SSRI, fluoxetine and sertraline, on pregnancy and neonatal outcomes in mice. Wild-type mice were treated daily with low and high doses of fluoxetine (2 and 20 mg/kg) and sertraline (10 and 20 mg/kg) from the day of detection of a vaginal plug until the end of lactation (21 days postpartum). Pregnancy rate was decreased only in the high dose of fluoxetine group. Maternal weight gain was reduced in the groups receiving the high dose of each drug. Number of pups born was decreased in the high dose of fluoxetine and low and high doses of sertraline while the number of pups weaned was decreased in all SSRI-treated groups corresponding to increased neonatal mortality in all SSRI-treated groups. In conclusion, there was a dose-dependent effect of SSRI on pregnancy and neonatal outcomes in a non-depressed mouse model. However, the distinct placental transfer of each drug suggests that the effects of SSRI on pup mortality may be mediated by SSRI-induced placental insufficiency rather than a direct toxic effect on neonatal development and mortality.

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Increased milking frequency and incomplete milking have differential effects on milk yield and mammary gland physiology that are important for optimization of milking practices in dairy herds. The objectives of this experiment were to determine the effects of increased milking frequency and incomplete milking on milk production rate (MPR) and milk composition and to determine if milking 3 times daily (3×) could rescue the negative production effects of incomplete milking. Twenty-two multiparous cows were enrolled onto this experiment beginning at 5 days in milk (DIM) and continuing through 47 DIM. A split-plot design was used to randomize the 2 treatments, which were milking frequency and incomplete milking. Eleven cows were randomly assigned to be milked 2 times (2×) daily and 11 cows were randomly assigned to be milked 3×. Within each cow, a contralateral half-udder was randomly assigned to be incompletely milked (30% milk remaining in the gland; IM), and the other half-udder was randomly assigned to be milked completely (CM). Quarter-level milk yields were recorded at each milking session. Milk samples from all quarters were collected twice weekly at the beginning of the morning milking for analysis. Cows milked 2× tended to have reduced MPR compared with 3× milked cows (1.81 ± 0.06 vs. 1.97 ± 0.06 kg milk/h; P = 0.06). Half-udders that were CM and IM produced 1.09 ± 0.03 and 0.80 ± 0.03 kg milk/h, respectively. There was an interaction between incomplete milking treatment and week of lactation (P = 0.04). No interaction was detected between milking frequency and incomplete milking for MPR or milk components. Cows milked 3× had increased milk fat percent (1.93 ± 0.09% vs. 1.65 ± 0.09%, P = 0.047), decreased milk lactose percent (4.80 ± 0.04% vs. 4.93 ± 0.04%, P = 0.04), and exhibited no differences in milk protein percent or milk somatic cell count (SCC) compared with cows milked 2×. Half-udders that were IM had increased milk fat percent (2.15 ± 0.07% vs. 1.43 ± 0.07%, P < 0.0001), decreased lactose percent (4.75 ± 0.03% vs. 4.99 ± 0.03%, P < 0.0001), increased milk log10SCC (4.22 ± 0.05 vs. 4.41 ± 0.05, P = 0.0004), and no differences in milk protein percent compared with CM half-udders. These results indicate that a 3× milking frequency in IM half-udders was not able to improve milk production compared with IM half-udders milked 2×. Our results indicate that 30% milk remaining in the gland had an irreversible impact on milk yield as increased milking frequency was not able to reverse the milk yield lost.

BackgroundSince hearing loss and cognitive decline often co-occur among older adults, a cognitive screening test suitable for hearing-impaired people is of high clinical relevance. We report the first evaluation of a German language version of the Montreal Cognitive Assessment—Hearing Impaired version (MoCA-HI).ObjectiveThe aim of the present study was to compare cognitively healthy participants with and without hearing loss, to examine the impact of age, sex, educational level and degree of hearing impairment on the German MoCA-HI performance, and to develop normative data.Material and methodsThe German MoCA-HI was tested in 94 participants with normal or mild hearing impairment (group 1: 4PTA ≤ 40 dB on the better hearing ear) and 81 participants with moderate to profound hearing loss (group 2: 4PTA > 40 dB on the better hearing ear). Additionally, all participants performed the standard MoCA (version 8.2).ResultsNo significant group difference between group 1 and 2 was found in the MoCA-HI total score (p = 0.05). In contrast, group 1 performed significantly better than group 2 on the standard MoCA (p < 0.001). There was no difference between the MoCA and the MoCA-HI performance in group 1 (p = 0.12), whereas individuals of group 2 performed significantly better on the MoCA-HI than on the standard MoCA (p < 0.001). Test-retest reliability of the MoCA-HI was high (p < 0.001). Higher age (p < 0.001), male sex (p = 0.009) and lower education (p < 0.001) were associated with a lower overall MoCA-HI score. Based on the demographic data normative data were developed by a regression-based approach.ConclusionThe MoCA-HI is a cognitive screening test which is suitable for people with hearing impairment.

BackgroundHearing loss and dementia are highly prevalent in older age and often co-occur. Most neurocognitive screening tests are auditory-based, and performance can be affected by hearing loss. To address the need for a cognitive screening test suitable for people with hearing loss, a visual version of the Montreal-Cognitive-Assessment was developed and recently validated in English (MoCA-H), with good sensitivity and specificity for identifying cases of dementia. As the MoCA is known to perform differently across languages, revalidation of the German MoCA-H was necessary. The aim of the present study was to assess the diagnostic accuracy of the German MoCA-H among those with normal cognition, mild cognitive impairment (MCI) and dementia and to determine an appropriate performance cut- off.Materials and methodsA total of 346 participants aged 60–97 years (M = 77.18, SD = 9.56) were included; 160 were cognitively healthy, 79 with MCI and 107 were living with dementia based on the GPCOG and a detailed medical questionnaire as well as a comprehensive examination by a neurologist in case of cognitive impairment. Performance cut-offs for normal cognition, MCI and dementia were estimated for the MoCA-H score and z-scores using the English MoCA-H cut-off, the balanced cut-off and the Youden’s Index.ResultsA mean score of 25.49 (SD = 3.01) points in the German MoCA-H was achieved in cognitively healthy participants, 20.08 (SD = 2.29) in the MCI and 15.80 (SD = 3.85) in the dementia group. The optimum cut-off for the detection of dementia was ≤21 points with a sensitivity of 96.3% and a specificity of 90%. In the MCI group, a cut-off range between 22 and 24 points is proposed to increase diagnostic accuracy to a sensitivity and specificity of 97.5 and 90%, respectively.ConclusionThe German MoCA-H seems to be a sensitive screening test for MCI and dementia and should replace commonly used auditory-based cognitive screening tests in older adults. The choice of a cut-off range might help to better reflect the difficulty in clinical reality in detecting MCI. However, screening test batteries cannot replace a comprehensive cognitive evaluation.