Clinical observations and management of a severe equine herpesvirus type 1 outbreak with abortion and encephalomyelitis

Latent equine herpesvirus type 1 (EHV-1) infection is common in horse populations worldwide and estimated to reach a prevalence nearing 90% in some areas. The virus causes acute outbreaks of disease that are characterized by abortion and sporadic cases of myeloencephalopathy (EHM), both severe threats to equine facilities. Different strains vary in their abortigenic and neuropathogenic potential and the simultaneous occurrence of EHM and abortion is rare. In this report, we present clinical observations collected during an EHV-1 outbreak caused by a so-called "neuropathogenic" EHV-1 G(2254)/D(752) polymerase (Pol) variant, which has become more prevalent in recent years and is less frequently associated with abortions. In this outbreak with 61 clinically affected horses, 6/7 pregnant mares aborted and 8 horses developed EHM. Three abortions occurred after development of EHM symptoms. Virus detection was performed by nested PCR targeting gB from nasal swabs (11 positive), blood serum (6 positive) and peripheral blood mononuclear cells (9 positive) of a total of 42 horses sampled. All 6 fetuses tested positive for EHV-1 by PCR and 4 by virus isolation. Paired serum neutralization test (SNT) on day 12 and 28 after the index case showed a significant (≥ 4-fold) increase in twelve horses (n = 42; 28.6%). This outbreak with abortions and EHM cases on a single equine facility provided a unique opportunity for the documentation of clinical disease progression as well as diagnostic procedures

Skin malformations in a neonatal foal tested homozygous positive for Warmblood Fragile Foal Syndrome

BACKGROUND: Skin malformations that resembled manifestations of Ehlers-Danlos-Syndrome were described in a variety of domestic animals during the last century as cutis hyperelastica, hyperelastosis cutis, dermatosparaxis, dermal/collagen dysplasia, dermal/cutaneous asthenia or Ehlers-Danlos-like syndrome/s. In 2007, the mutation responsible for Hereditary Equine Regional Dermal Asthenia (HERDA) in Quarter Horses was discovered. Several case reports are available for similar malformations in other breeds than Quarter Horses (Draught Horses, Arabians, and Thoroughbreds) including four case reports for Warmblood horses. Since 2013, a genetic test for the Warmblood Fragile Foal Syndrome Type 1 (WFFS), interrogating the causative point mutation in the equine procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1, or lysyl hydroxylase 1) gene, has become available. Only limited data are available on the occurrence rate and clinical characteristics of this newly detected genetic disease in horses. In humans mutations in this gene are associated with Ehlers-Danlos Syndrome Type VI (kyphoscoliotic form). CASE PRESENTATION: This is the first report describing the clinical and histopathological findings in a foal confirmed to be homozygous positive for WFFS. The Warmblood filly was born with very thin, friable skin, skin lesions on the legs and the head, and an open abdomen. These abnormalities required euthanasia just after delivery. Histologic examination revealed abnormally thin dermis, markedly reduced amounts of dermal collagen bundles, with loosely orientation and abnormally large spaces between deep dermal fibers. CONCLUSION: WFFS is a novel genetic disease in horses and should be considered in cases of abortion, stillbirth, skin lesions and malformations of the skin in neonatal foals. Genetic testing of suspicious cases will contribute to evaluate the frequency of occurrence of clinical WFFS cases and its relevance for the horse population

Quantification of friction force reduction induced by obstetric gels

The objective of this study was to quantify the reduction of friction forces by obstetric gels aimed to facilitate human childbirth. Lubricants, two obstetric gels with different viscosities and distilled water, were applied to a porcine model under mechanical conditions comparable to human childbirth. In tests with higher movement speeds of the skin relative to the birth canal, both obstetric gels significantly reduced dynamic friction forces by 30-40% in comparison to distilled water. At the lowest movement speed, only the more viscous gel reduced dynamic friction force significantly. In tests modifying the dwell time before a movement was initiated, static friction forces of trials with highly viscous gel were generally lower than those with distilled water. The performed biomechanical tests support the recommendation of using obstetric gels during human childbirth. Using the presented test apparatus may reduce the amount of clinical testing required to optimize gel formulatio

Obstetric gel shortens second stage of labor and prevents perineal trauma in nulliparous women: a randomized controlled trial on labor facilitation

Objective: To determine whether the obstetric gel shortens the second stage of labor and exerts a protective effect on the perineum. Method: A total of 251 nulliparous women with singleton low-risk pregnancies in vertex position at term were recruited. A total of 228 eligible women were randomly assigned to Group A, without obstetric gel use, or to Group B, obstetric gel use, i.e., intermittent application into the birth canal during vaginal examinations, starting at the early first stage of labor (prior to 4cm dilation) and ending with delivery. Results: A total of 183 cases were analyzed. For vaginal deliveries without interventions, such as C-section, vaginal operative procedure or Kristeller maneuver, obstetric gel use significantly shortened the second stage of labor by 26min (30%) (P=0.026), and significantly reduced perineal tears (P=0.024). First stage of labor and total labor duration were also shortened, but not significantly. Results did not show a significant change in secondary outcome parameters, such as intervention rates or maternal and newborn outcomes. No side effects were observed with obstetric gel use. Conclusion: Systematic vaginal application of obstetric gel showed a significant reduction in the second stage of labor and a significant increase in perineal integrity. Future studies should further investigate the effect on intervention rates and maternal and neonatal outcome parameter

Differentiation of mouse embryonic stem cells into cells with spermatogonia-like morphology with chemical intervention-dependent increased gene expression of LIM homeobox 1 (Lhx1)

Spermatogonial stem cells (SSCs) originate from gonocytes that differentiate from primordial germ cells (PGCs). In the developing mouse testis, expression of the gene LIM homeobox 1 (Lhx1) marks the most undifferentiated SSCs, which has not yet been reported for spermatogonia-like cells generated in vitro. Previously, it was shown that a chemical intervention in male mouse embryonic stem (ES) cells in serum culture, including Sirtuin 1 (SIRT1) inhibitor Ex-527, DNA methyltransferase (DNMT) inhibitor RG-108 and electrophilic redox cycling compound tert-butylhydroquinone (tBHQ), was associated with molecular markers of PGC to gonocyte differentiation. Here, we report the in vitro differentiation of male mouse ES cells, cultured under dual chemical inhibition of GSK3β and MEK (2i) with leukemia inhibitory factor (LIF) (2iL) and serum, into cells with spermatogonia-like morphology (CSMs) and population-averaged expression of spermatogonia-specific genes by removal of 2iL and a specific schedule of twice daily partial medium replacement. Combination of this new protocol with the previously reported chemical intervention increased population-averaged gene expression of Lhx1 in the resulting CSMs. Furthermore, we detected single CSMs with strong nuclear LHX1/5 protein signal only in the chemical intervention group. We propose that further investigation of CSMs may provide new insights into male germline development

Interrogating the Diversity of Vaginal, Endometrial, and Fecal Microbiomes in Healthy and Metritis Dairy Cattle

The bovine genital tract harbors a dynamic microbiome. Genital tract microbial communities in healthy animals have been characterized using next-generation sequencing methods showing that microbe compositions differ between the vagina and uterus, more so during the postpartum period. Pre-calving fecal and vaginal, and endometrial swabs at the different postpartum intervals were collected from dairy cows. Microbiomes in these samples were determined based on bacterial 16S amplicon sequencing and compared between healthy (H; n = 10) control animals and cows that developed metritis (M; n = 10) within 21 days postpartum (DPP). Compared to healthy animals the pre-calving fecal and vaginal microbiomes of metritis animals were more abundant in sequences from the phylum Fusobacteria and the bacterial genera such as Escherichia-Shigella and Histophilus. In addition, compared to healthy animals, metritis cows harboured low microbial species diversity in the endometrium, as well as decreasing Proteobacteria and increasing Fusobacteria, Firmicutes, Actinobacteria, and Bacteroidetes abundances. The greatest taxonomic compositional deviations in endometrial microbial communities between the metritis and health cows were detected between 7 and 10 DPP. There was high taxonomic similarity detected between postpartum endometrial microbiomes and the prepartum vaginal and fecal microbiomes suggesting that colonization through bacteria ascending from the rectum and vagina to the uterine cavity might play a major role in establishing the endometrial microbiome postpartum. A deeper understanding of the establishment and dynamics of postpartum endometrial microbial communities in cows will thus provide crucial basic knowledge to guide the development of genital microbiome manipulation strategies for preventing uterine disease and improving fertility in dairy cows

Differentiation of mouse embryonic stem cells into cells with spermatogonia-like morphology with chemical intervention-dependent increased gene expression of LIM homeobox 1 (Lhx1).

Spermatogonial stem cells (SSCs) originate from gonocytes that differentiate from primordial germ cells (PGCs). In the developing mouse testis, expression of the gene LIM homeobox 1 (Lhx1) marks the most undifferentiated SSCs, which has not yet been reported for spermatogonia-like cells generated in vitro. Previously, it was shown that a chemical intervention in male mouse embryonic stem (ES) cells in serum culture, including Sirtuin 1 (SIRT1) inhibitor Ex-527, DNA methyltransferase (DNMT) inhibitor RG-108 and electrophilic redox cycling compound tert-butylhydroquinone (tBHQ), was associated with molecular markers of PGC to gonocyte differentiation. Here, we report the in vitro differentiation of male mouse ES cells, cultured under dual chemical inhibition of GSK3β and MEK (2i) with leukemia inhibitory factor (LIF) (2iL) and serum, into cells with spermatogonia-like morphology (CSMs) and population-averaged expression of spermatogonia-specific genes by removal of 2iL and a specific schedule of twice daily partial medium replacement. Combination of this new protocol with the previously reported chemical intervention increased population-averaged gene expression of Lhx1 in the resulting CSMs. Furthermore, we detected single CSMs with strong nuclear LHX1/5 protein signal only in the chemical intervention group. We propose that further investigation of CSMs may provide new insights into male germline development

Effects of meteorological factors and the lunar cycle on onset of parturition in cows

The present paper summarizes a comprehensive retrospective study that was undertaken to investigate effects of meteorological factors and lunar cycle on gestation length and daily birth rate in cows. To this end, all cattle births in Switzerland between 2008 and 2010 (n=2,091,159) were related to detailed matched weather recordings. The study revealed some statistically significant effects of climate (temperature, barometric pressure, relative humidity) and weather (thunderstorms, heat index) on gestational length. Thunderstorms on the day before birth reduced the gestation length by 0.5 days. An increase in the birth rate was correlated with the temperature on the day before birth and the barometric pressure 3 days before birth. Differences in the barometric pressure >15hPa increased the birth rate by 4%. Nevertheless, the effects were not consistent and the modeled size of effect was so small that a clinical implication is unlikely. Although the daily birth rate was unevenly distributed across the lunar cycle, no clear pattern could be identified. Compared to the mean birth rate across the lunar cycle the highest daily birth rate was detected on day 4 after new moon (+1.9%) and the lowest on day 20 (-2.1%)

Assessment of Postnatal Pulmonary Adaption in Bovine Neonates Using Electric Impedance Tomography (EIT)

Several aspects of postnatal pulmonary adaption in the bovine neonate remain unclear, particularly the dynamics and regional ventilation of the lungs. We used electric impedance tomography (EIT) to measure changes in ventilation in the first 3 weeks of life in 20 non-sedated neonatal calves born without difficulty in sternal recumbency. Arterial blood gas variables were determined in the first 24 h after birth. Immediately after birth, dorsal parts of the lungs had 4.53% ± 2.82% nondependent silent spaces (NSS), and ventral parts had 5.23% ± 2.66% dependent silent spaces (DSS). The latter increased in the first hour, presumably because of gravity-driven ventral movement of residual amniotic fluid. The remaining lung regions had good ventilation immediately after birth, and the percentage of lung regions with high ventilation increased significantly during the study period. The centre of ventilation was always dorsal to and on the right of the theoretical centre of ventilation. The right lung was responsible for a significantly larger proportion of ventilation (63.84% ± 12.74%, p < 0.00001) compared with the left lung. In the right lung, the centrodorsal lung area was the most ventilated, whereas, in the left lung, it was the centroventral area. Tidal impedance changes, serving as a surrogate for tidal volume, increased in the first 3 weeks of life (p < 0.00001). This study shows the dynamic changes in lung ventilation in the bovine neonate according to EIT measurements. The findings form a basis for the recognition of structural and functional lung disorders in neonatal calves