Autosomal recessive hyposegmentation of granulocytes in Australian Shepherd Dogs indicates a role for LMBR1L in myeloid leukocytes.

Pelger-Huët anomaly (PHA) in humans is an autosomal dominant hematological phenotype without major clinical consequences. PHA involves a characteristic hyposegmentation of granulocytes (HG). Human PHA is caused by heterozygous loss of function variants in the LBR gene encoding lamin receptor B. Bi-allelic variants and complete deficiency of LBR cause the much more severe Greenberg skeletal dysplasia which is lethal in utero and characterized by massive skeletal malformation and gross fetal hydrops. HG phenotypes have also been described in domestic animals and homology to human PHA has been claimed in the literature. We studied a litter of Australian Shepherd Dogs with four stillborn puppies in which both parents had an HG phenotype. Linkage analysis excluded LBR as responsible gene for the stillborn puppies. We then investigated the HG phenotype in Australian Shepherd Dogs independently of the prenatal lethality. Genome-wide association mapped the HG locus to chromosome 27 and established an autosomal recessive mode of inheritance. Whole genome sequencing identified a splice site variant in LMBR1L, c.191+1G>A, as most likely causal variant for the HG phenotype. The mutant allele abrogates the expression of the longer X2 isoform but does not affect transcripts encoding the shorter X1 isoform of the LMBR1L protein. The homozygous mutant LMBR1L genotype associated with HG is common in Australian Shepherd Dogs and was found in 39 of 300 genotyped dogs (13%). Our results point to a previously unsuspected function of LMBR1L in the myeloid lineage of leukocytes.

Prevalence, incidence and treatment patterns of prurigo nodularis in England: a retrospective database analysis.

BACKGROUND: Prurigo nodularis (PN) is a pruritic skin disease characterized by multiple intensely itchy skin nodules in symmetrically distributed areas of the extremities. There are limited studies on the epidemiology and treatment pathways of PN, especially moderate-to-severe PN, from England. OBJECTIVES: To assess the epidemiology and treatment pathways of mild and moderate-to-severe PN in England. METHODS: This retrospective cohort study used data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England. Adult patients (aged ≥ 18 years) with a PN-specific diagnosis code allocated any time between 1 April 2007 and 1 March 2019 (patient identification period) were selected. Patients were included if their first PN diagnostic code (index diagnosis date; IDD) was recorded during the identification period, with data available 6 months before and ≥ 12 months after the IDD. Patients were classified as having moderate-to-severe PN (MSPN) or mild PN (MiPN), based on the presence or absence of a prescription record, post-IDD, for either a systemic immunosuppressant or a gabapentinoid. Patients with MSPN and MiPN were matched 1 : 1 according to age, sex and IDD. Prevalence and incidence were calculated for each year from 2007 to 2019. Drugs prescribed post-IDD were analysed. RESULTS: A total of 8933 patients (MSPN, n = 2498; MiPN, n = 6435) were included in the study; 2462 patients with MiPN and 2462 with MSPN were included for the comparative analysis. The presence of atopic dermatitis, asthma and eosinophilic oesophagitis were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN. The overall prevalence of cases of PN increased during the study period. The incidence rate also showed a similar trend. The rates of prescription of potent and super-potent topical corticosteroids (TCS), topical calcineurin inhibitors, first- and second-generation antihistamines, oral and injectable systemic corticosteroids, methotrexate, antidepressants and tacrolimus were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN. CONCLUSIONS: The epidemiology of PN was consistent with that found in other European studies. Patients with MSPN received a significantly higher number of prescriptions for potent TCS and systemic drugs compared with patients with MiPN.

Prurigo nodularis is an itchy skin disease that can affect a person's daily life and sleep, and is often accompanied by other diseases. Skin ointments are used to treat the disease. If these are not effective, the disease is treated with oral medicine. The severity of prurigo nodularis is not well established. People with prurigo nodularis and treated with skin ointments are generally considered to have a milder form of the disease. Patients with severe disease most often require oral medicine that target the immune system. In England, there are no estimates of how often prurigo nodularis has affected the population over the last 10 years. In this study, we looked at cases of mild and moderate-to-severe prurigo nodularis in England and the treatments used by patients. We found that cases of prurigo nodularis (both mild and moderate-to-severe) increased during the study period, which was 2007 to 2019. Patients with the more severe form of the disease were more often treated with drugs that were not approved for treating it. Overall, our findings suggest that the number of patients with prurigo nodularis is increasing in England. A new and approved treatment option might be required to manage moderate-to-severe disease.

Comparison of two-dimensional (2D) and three-dimensional (3D) ultrasonography for gestational ageing in the early to mid-pregnant bitch.

Accuracy of prediction of the day of parturition in the bitch decreases with advancing pregnancy. We hypothesized that three-dimensional (3D) volume ultrasonography may be superior for gestational ageing than 2D measurements. Thirty-two pregnancy examinations were performed in 25 bitches of different breeds 21-34 days after the first mating. Ovulation date from serum progesterone concentrations was estimated for 15 bitches, and parturition date was recorded for all dogs. Inner chorionic cavity (ICC) diameters and ICC length of the conceptus were measured by 2D B-mode, and ICC volume by 3D ultrasonography (Voluson® i, GE Healthcare). Linear or exponential regressions between ICC measurements and time, i.e. days after estimated ovulation or days before parturition, were performed with significance set at p < .05. ICC volume increased exponentially over time, while ICC diameter showed a linear growth. ICC volume had similar accuracy (R2  = .718, p < .001) to ICC diameter and ICC length (R2  = .707 and R2  = .728, p < .001) when analysed in relation to days after estimated ovulation or in relation to days before parturition (R2  = .818, R2  = .800 and R2  = .810, p < .001 respectively). There were strong (R2  ≥ .875) significant associations between all ICC measurements. In conclusion, ICC volume did not improve canine gestational ageing accuracy, which supports the continued use of the ICC diameter, particularly in light of the difficulty in obtaining 3D measurements. On the basis of ICC volume, the growth of the canine conceptus appeared to be exponential already during the first half of pregnancy.

Involvement of Oxytocin and Progesterone Receptor Expression in the Etiology of Canine Uterine Inertia.

An altered oxytocin and progesterone receptor (OXTR and PGR, respectively) expression was postulated in canine uterine inertia (UI), which is the lack of functional myometrial contractions. OXTR and PGR expressions were compared in uterine tissue obtained during C-section due to primary UI (PUI; n = 12) and obstructive dystocia (OD, n = 8). In PUI, the influence of litter size was studied (small/normal/large litter: PUI-S/N/L: n = 5/4/3). Staining intensity in immunohistochemistry was scored for the longitudinal and circular myometrial layer and summarized per dog (IP-Myoscore). Mean P4 did not differ significantly between PUI (n = 9) and OD (n = 7). OXTR and PGR expressions (ratios) were significantly higher in PUI (OXTR: p = 0.0019; PGR: p = 0.0339), also for OXTR in PUI-N versus OD (p = 0.0034). A trend for a higher PGR IP-Myoscore was identified (PUI-N vs. OD, p = 0.0626) as well as an influence of litter size (lowest PGR-Myoscore in PUI-L, p = 0.0391). In conclusion, PUI was not related to higher P4, but potentially increased PGR availability compared to OD. It remains to be clarified whether OXTR is upregulated in PUI due to a counterregulatory mechanism to overcome myometrial quiescence or downregulated in OD due to physiological slow OXTR desensitization associated with an advanced duration of labor. Identified OXTR differences between myometrial layers indicate the need for further research.

Do uterine PTGS2, PGFS, and PTGFR expression play a role in canine uterine inertia?

The aetiology of primary uterine inertia (PUI), which is the most common cause of canine dystocia, is still not elucidated. Prostaglandins (PGs) play a crucial role in parturition. We hypothesized that the expression of prostaglandin endoperoxidase synthase 2 (PTGS2), PGF2α synthase (PGFS), and corresponding receptor (PTGFR) is altered in PUI. We investigated PTGS2, PGFS, and PTGFR mRNA expression, and PTGS2 and PGFS protein expression in interplacental (IP) and uteroplacental sites (UP) in bitches with PUI, obstructive dystocia (OD), and prepartum (PC). PTGS2, PGFS, and PTGFR mRNA expression did not differ significantly between PUI and OD (IP/UP). PTGFR ratio in UP was higher in PC than in OD (p = 0.014). PTGS2 immunopositivity was noted in foetal trophoblasts, luminal and superficial glandular epithelial cells, smooth muscle cells of both myometrial layers, and weakly and sporadically in deep uterine glands. PGFS was localized in luminal epithelial cells and in the epithelium of superficial uterine glands. PTGS2 and PGFS staining was similar between PUI and OD, while PGFS protein expression differed between OD and PC (p = 0.0215). For PTGS2, the longitudinal myometrial layer of IP stained significantly stronger than the circular layer, independent of groups. These results do not support a role for PTGS2, PGFS, and PTGFR in PUI. Reduced PGFS expression in IP during parturition compared with PC and the overall lack of placental PGFS expression confirm that PGFS is not the main source of prepartal PGF2alpha increase. The difference in PTGS2 expression between IP myometrial layers warrants further investigation into its physiological relevance.

Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog.

The underlying functional and molecular changes in canine primary uterine inertia (PUI) are still not clarified. Leptin (Lep) and obesity negatively affect uterine contractility in women, partly mediated by the RhoA/Rho associated kinase pathway, affecting myometrial calcium sensitization. We hypothesized that increased uterine Lep/Lep receptor (LepR) or decreased RhoA/Rho associated kinase expression contributes to PUI in dogs, independent of obesity. Dogs presented for dystocia were grouped into PUI (n = 11) or obstructive dystocia (OD, still showing strong labor contractions; n = 7). Interplacental full-thickness uterine biopsies were collected during Cesarean section for relative gene expression (RGE) of RhoA, its effector kinases (ROCK1, ROCK2), Lep and LepR by qPCR. Protein and/or mRNA expression and localization was evaluated by immunohistochemistry and in situ hybridization. RGE was compared between groups by one-way ANOVA using body weight as covariate with statistical significance at P < 0.05. Uterine ROCK1 and ROCK2 gene expression was significantly higher in PUI than OD, while RhoA and Lep did not differ. LepR RGE was below the detection limit in five PUI and all OD dogs. Litter size had no influence. Lep, LepR, RhoA, ROCK1, ROCK2 protein and/or mRNA were localized in the myometrium and endometrium. Uterine protein expression appeared similar between groups. LepR mRNA signals appeared stronger in PUI than OD. In conclusion, lasting, strong labor contractions in OD likely resulted in downregulation of uterine ROCK1 and ROCK2, contrasting the higher expression in PUI dogs with insufficient contractions. The Lep-LepR system may affect uterine contractility in non-obese PUI dogs in a paracrine-autocrine manner.

Evaluation of porcine semen quality by portable and desktop CASA systems - Short communication.

When using artificial insemination in porcine reproduction, one of the most important requirements is the suitable quality of semen regarding its total motility (TM) and progressive motility (PM). Computer-assisted sperm analysis (CASA) is an appropriate method to analyse the quality of semen. Recently a portable instrument has been developed to help specialists in their everyday field work. In our study, semen quality was measured simultaneously by the portable device (Ongo) and a laboratory CASA system (Microptic) to compare TM and PM values obtained by these appliances at a concentration of 50 × 106 spermatozoa/mL. Agreement between measurements was evaluated with a Bland-Altman plot. Strong correlation was found between the investigated instruments for all the three parameters, i.e. sperm concentration, TM and PM. However, a few measurements fell outside the defined range of acceptance.

Image Quality of Prospectively ECG-Triggered Coronary CT Angiography in Heart Transplant Recipients.

OBJECTIVE: Cardiac allograft vasculopathy (CAV) is among the top causes of death 1 year after heart transplantation (HTx). Coronary CT angiography (CTA) is a potential alternative to invasive imaging in the diagnosis of CAV. However, the higher heart rate (HR) of HTx recipients prompts the use of retrospective ECG-gating, which is associated with higher radiation dose, a major concern in this patient population. Therefore, we sought to evaluate the feasibility and image quality of low-radiation-dose prospectively ECG-triggered coronary CTA in HTx recipients. MATERIALS AND METHODS: In total, 1270 coronary segments were evaluated in 50 HTx recipients and 50 matched control subjects who did not undergo HTx. The control subjects were selected from our clinical database and were matched for age, sex, body mass index, HR, and coronary dominance. Scans were performed using 256-MDCT with prospective ECG-triggering. The degree of motion artifacts was evaluated on a per-segment basis on a 4-point Likert-type scale. RESULTS: The median HR was 74.0 beats/min (interquartile range [IQR], 67.8-79.3 beats/min) in the HTx group and 73.0 beats/min (IQR, 68.5-80.0 beats/min) in the matched control group (p = 0.58). In the HTx group, more segments had diagnostic image quality compared with the control group (624/662 [94.3%] vs 504/608 [82.9%]; p < 0.001). The mean effective radiation dose was low in both groups (3.7 mSv [IQR, 2.4-4.3 mSv] in the HTx group vs 4.3 mSv [IQR, 2.6-4.3 mSv] in the control group; p = 0.24). CONCLUSION: Prospectively ECG-triggered coronary CTA examinations of HTx recipients yielded diagnostic image quality with low radiation dose. Coronary CTA is a promising noninvasive alternative to routine catheterization during follow-up of HTx recipients to diagnose CAV.

Expression of insulin-like growth factor 1 and its receptor in preovulatory follicles and in the corpus luteum in the bitch.

In the bitch, ovarian follicular and corpus luteum (CL) development and function are regulated by gonadotropins as well as local factors, the role of which is especially important during the early CL phase of relative gonadotrophic independence. We assumed that insulin-like growth factor 1 (IGF1) has a paracrine/autocrine regulatory role in ovarian follicular and luteal function in the dog. To address our hypothesis, we studied gene and protein expression of IGF1 and its receptor (IGF1R) in preovulatory follicles and in the CL of pregnant and non-pregnant dogs, and following antigestagen (aglepristone, progesterone receptor blocker) treatment in mid-gestation. Ovaries in the follicular phase were collected from five bitches. CL were collected on pregnancy Days 8-12 (pre-implantation), 18-25 (post-implantation), 35-40 (mid-gestation), at prepartum luteolysis, and 24 h and 72 h after aglepristone treatment in mid-gestation (n = 3-5 per group). From non-pregnant bitches, CL were collected on Days 5, 15, 25, 35, 45, 65 after ovulation (n = 4-5 per group). Semi-quantitative real-time (TaqMan) PCR and immunohistochemistry were applied. IGF1 immunostaining in preovulatory follicles seemed stronger in theca interna than granulosa cells. IGF1R signals appeared more intense in granulosa cells at the apical part of mural folds. In pregnant dogs, luteal IGF1 mRNA expression decreased significantly from pre-implantation to prepartum luteolysis, while IGF1R expression increased at prepartum luteolysis. Aglepristone treatment in mid-gestation had no effect on IGF1 and IGF1R mRNA levels. In non-pregnant bitches, highest IGF1 mRNA concentrations were found in the early CL and decreased by Days 45 and 65, while IGF1R expression did not change. In the CL of pregnant bitches, signals for IGF1 and IGF1R in luteal cells were strongest at pre- and post-implantation and weakest at prepartum luteolysis. IGF1 and IGF1R immunostaining was also detected in macrophages and in blood vessels. In conclusion, IGF1 may have a paracrine or autocrine role in granulosa and theca interna cells in preovulatory follicles. As IGF1 was highest represented in early luteal stages in pregnant and non-pregnant bitches, this may support a role for IGF1 in steroid synthesis, angiogenesis and cell proliferation as well as in immune function in the early canine CL. The unaffected mRNA levels after aglepristone treatment may support that IGF1 is not directly regulated by local progesterone in an auto- or paracrine manner.

The influence of spaying and its timing relative to the onset of puberty on urinary and general behaviour in Labrador Retrievers.

Benefits and risks of spaying on the behaviour of female dogs are controversially discussed. Increased aggressiveness and male urinary behaviour were postulated to be the consequence of masculinization after spaying in some female dogs. To investigate if spaying or its timing relative to the onset of puberty may have a masculinization effect, urinary behaviour, that is, frequency of urination, urinary posture and ground scratching after urination were recorded in 58 female Labrador Retrievers during 15 min of a daily walk with their owners. General behaviour of the dogs during the walks was assessed using an owner questionnaire. Data were analysed for age, reproductive status, lifetime of ovary exposure and/or time interval since spaying. Urinary behaviour of intact females (n = 12) and dogs spayed before (n = 17) or after (n = 29) puberty was similar and not influenced by age, lifetime of ovary exposure and/or time interval since spaying. Owners of spayed dogs described more frequent or more intense fear reaction in their animals in response to loud noises, unfamiliar objects approaching on or near the sidewalk, or if they were approached by unknown dogs barking, growling or jumping. In conclusion, we found no evidence of a masculinization effect after spaying on urinary behaviour in female Labrador Retrievers. In contrast to popular belief, gonadectomy did not inevitably result in a behaviourally more stable dog. Extrapolation of our findings from female Labrador Retrievers to other breeds should be performed with caution, as the effect of spaying on behaviour may differ among dog breeds.

Detection of pregnancy in sheep using an ELISA for pregnancy-specific protein B.

The early detection of pregnancy and the determination of fetal numbers have economic benefits in sheep production because of the seasonal breeding patterns where missing a breeding opportunity means the loss of one productive year. The purpose of this study was to evaluate the efficacy of the B6-HRP ELISA for ovine pregnancy-specific protein B (oPSPB) measurement in the detection of pregnancy and estimation of fetal numbers in different sheep breeds. BioPRYN® ELISA assay kit was used for the detection of pregnancy in the experimental animals. Ninety-three ewes of three breeds (British Milksheep - BM, Lacaune - L and Transylvanian Racka - TR), each from three farms in Hungary, were included in the study. BM and L ewes were artificially inseminated (AI). Thirty-five days after AI, all ewes were examined by transabdominal ultrasound. The TR flock was mated naturally over a six-week period. At the end of the mating period, the ewes were similarly examined by ultrasound. Blood samples were taken from all pregnant ewes twice (35 and 65 days after AI), and serum samples were assayed by the BioPRYN test. It can be concluded that the detection of serum PSPB by ELISA is a much easier, safer, less expensive and highly accurate method for the detection of ovine pregnancy. Although some breed-related differences were detectable at 35 and 65 days post breeding, no differences in oPSPB levels were found in pregnant ewes carrying different numbers of fetuses.

Is twin pregnancy, calving and pregnancy loss predictable by serum pregnancy-specific protein b (pspb) concentration 28-35 days after ai in dairy cows?

Double ovulation occurs more frequently in multiparous cows with high milk production than in primiparous cows and the rate of twin pregnancy/calving is increasing worldwide. Diagnosis of twin pregnancy is possible by ultrasound at the time of early pregnancy examination [28-34 days after artificial insemination (AI)]. Pregnancy proteins are also well-known indicators of gestation. The risk of pregnancy loss during the first trimester of gestation for cows carrying twins is three to nine times higher than for cows carrying singletons. Pregnancy-specific protein B (PSPB) is a good indicator not only of pregnancy but also of pregnancy loss. The aims of this study were (a) to collect calving data in some Hungarian Holstein-Friesian herds (n = 7,300) to compare PSPB serum concentrations (measured 29-35 days post insemination) in twin- and singleton-calving cows (Trial 1), and (b) to check the predictive value of PSPB serum concentration for twin pregnancy and pregnancy loss in high-producing Spanish Holstein-Friesian cows (n = 98; Trial 2). Our results showed almost 7% twin calving rate. Although hormonal treatments are commonly believed to be major causes of twin pregnancies, our data do not support this hypothesis. The only exception is the single PGF injection, which significantly increased twin calving. No effect of milk production on the risk of twin pregnancy was found, and twin pregnancy increased with parity. The AI bull, the bull's sire, the bull's grandfather and the cow's father also affected twin calving (P ≤ 0.02). We found much higher frequency of twin calving in cows diagnosed pregnant with higher than 3 ng/ml serum PSPB concentrations at 29-35 days after insemination. In Trial 2, non-significant but well-marked differences were found in PSPB serum concentration between singleton- and twin-pregnant cow samples (2.1 and 2.9 ng/ml) at different bleeding times. Probably the small size of the study population and the effects of milk production on PSPB values may explain this lack of significance.

Leptin in the canine uterus and placenta: possible implications in pregnancy.

BACKGROUND: Leptin (Lep) is known for its involvement in the regulation of reproductive functions. It is important for uterine receptivity, implantation, placental growth and maternal energy homeostasis in several species, but Lep's function in the pregnant dog has not been investigated. METHODS: Pregnant bitches were ovariohysterectomized at pre-implantation, post-implantation, mid-gestation and prepartum luteolysis. Two additional groups were treated with aglepristone in mid-gestation, and ovariohysterectomized 24 or 72 h later. Lep and leptin receptor (LepR) gene expression was detected by semi-quantitative real-time PCR in pre-implantation and inter-placental uterine sections (Ut) and in utero-placental compartments (Ut/Pl). Immunohistochemistry and in situ hybridization (ISH) were performed for Lep and LepR protein and mRNA localization. Parametric one-way ANOVA, paired t-test and Wilcoxon signed-rank test were used for statistical analysis. RESULTS: In the Ut/Pl, Lep expression was higher at post-implantation and prepartum luteolysis than at mid-gestation, while in the Ut, Lep mRNA levels did not change during pregnancy. LepR expression in the Ut/Pl was up-regulated at prepartum luteolysis compared to the earlier stages. In the Ut, highest LepR mRNA was found at pre- and post-implantation. LepR expression was down-regulated in the Ut/Pl compared to the Ut at post-implantation and at mid-gestation. Aglepristone treatment resulted in a decrease of Lep mRNA levels from 24 to 72 h in the Ut without concomitant changes in the Ut/Pl or in LepR levels. Lep and LepR immunoreactivities were strong in the luminal and glandular epithelium in the Ut with abundant LepR signals in the subepithelial stroma. In the Ut/Pl, fetal trophoblasts stained stronger for Lep and LepR than decidual cells, and signals for both proteins were also detected in the glandular chambers. The myometrium, blood vessel media, and sporadically also the endothelium stained for Lep and LepR. ISH showed similar signal distribution in the Ut and Ut/Pl. CONCLUSIONS: Lep and LepR are differentially expressed in the canine uterus and placenta during pregnancy, and their presence in various cell types indicates paracrine/autocrine roles. The Lep signaling system may be one of the pathways involved in feto-maternal cross-talk, implantation and maintenance of pregnancy, and may have a regulatory role around parturition.

Endocrine control of canine mammary neoplasms: serum reproductive hormone levels and tissue expression of steroid hormone, prolactin and growth hormone receptors.

BACKGROUND: Neoplasms of the mammary gland are among the most common diseases in female domestic dogs (Canis familiaris). It is assumed that reproductive hormones influence tumorigenesis in this species, although the precise role of the endocrine milieu and reproductive state is subject to continuing discussion. In line with this, a recent systematic review of available data on the development of mammary neoplasms revealed weak evidence for risk reduction after neutering and an effect of age at neutering. Investigation of several hormone receptors has revealed decreased expression of estrogen receptor-alpha (ERα, ESR1), progesterone (P4) receptor (PGR), prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) associated with neoplastic differentiation of mammary tissues. In other studies, increased levels of estrogens, progesterone and prolactin were found in serum and/or tissue homogenates of dogs with malignant neoplasms. However, the association between these entities within one animal population was never previously examined. Therefore, this study investigated the association between circulating serum concentrations of estradiol-17ß, progesterone and prolactin, and gene expression of ERα (ESR1), ERß (ESR2), PGR, PRLR, PRL and GHR, with respect to reproductive state (spayed vs. intact) and cycle stage (anestrus vs. diestrus). Additionally, the expression of E-cadherin (CDH-1) was evaluated as a possible indicator of metastatic potential. RESULTS: For all receptors, the lowest gene expression was found in malignant tumors compared to normal tissues of affected dogs. Steroid levels were not influenced by their corresponding receptor expression in mammary neoplasms, but increased PRL levels were negatively associated with low PRLR gene expression in malignant tumors. The expression of CDH-1 was influenced by tumor malignancy and cycle stage, i.e., the highest gene expression was found in benign mammary tumors in diestrous dogs compared to normal and malignant mammary tissues of anestrous and spayed dogs. CONCLUSIONS: Herein, it has been confirmed that transformation towards malignant neoplasms is associated with significant reduction of gene expression of particular hormone receptors. Only PRLR in malignant tumors seems to be influenced by circulating PRL levels. In dogs, CDH-1 can be used as a prognostic factor; its expression, however, in benign tumors is influenced by cycle stage.

Macroscopic and histological characteristics of fluid-filled ovarian structures in dairy cows.

The primary objective of this study was to use macroscopic and histological features of corpora lutea with a cavity and anovulatory cystic ovarian structures, present in 90 pairs of abattoir-derived dairy cow ovaries, as the basis to clarify the nomenclature of ovarian structures. Excluding morphologically normal ovarian fol-licles (antrum < 2 cm, wall < 1 mm), there were 27 fluid-filled ovarian structures. Ovulatory structures > 16 mm in diameter were designated as Group A (cavity ≤ 10 mm and wall > 10 mm) or Group B (cavity > 10 mm and wall < 10 mm). The volume of luteal tissue was less (P < 0.05) in Group B than in Group A, whereas that of a solid corpus luteum (CL) was intermediate (least square means ± SEM: 72 ± 1.92, 11.22 ± 1.57 and 5.84 ± 1.92 cm3, respectively). There was a greater proportion (P < 0.05) of small luteal cells in Group B compared to a solid CL, whereas Group A was intermediate (58.6 ± 5.3, 37.4 ± 5.3 and 44.0 ± 4.4%, respectively). Connective tissue was thicker (P < 0.05) in Group B than in Group A (295.4 ± 46.9 vs. 153.9 ± 38.2 µm). Based on the above-mentioned characteristics and differences, Groups A and B were designated as a CL with a cavity and a cystic CL, respectively. Furthermore, there were three groups of anovulatory ovarian structures. Structures in Group C were termed persistent/anovulatory follicles (overall diameter and wall thickness ≤ 20 and 1-3 mm, respectively). Finally, Groups D and E were designated as a follicle-fibrous cyst and a follicle-luteinised cyst (based on histological structure) for anovulatory structures with an overall diameter and wall thickness of ≥ 20 and ≤ 3 mm, and ≥ 20 and ≥ 3 mm, respectively.

[Disease burden of psoriasis associated with psoriatic arthritis in Hungary]. / Arthritis psoriaticával társuló középsúlyos és súlyos psoriasis betegségterhe Magyarországon.

INTRODUCTION: Psoriasis is a frequent, chronic, systemic immune-mediated disease mainly affecting the skin and joints. AIM: To assess health related quality of life and cost-of-illness in moderate to severe psoriasis associated with psoriatic arthritis. METHOD: A cross-sectional questionnaire survey was conducted at two academic dermatology clinics in Hungary. RESULTS: Fifty-seven patients (65% males) completed the survey with a mean age of 54.3±11.6 years and mean EQ-5D score of 0.48±0.4. Mean annual total cost was €8,977 per patient, of which 71% occurred due to biological therapy and 21% were indirect costs, respectively. Permanent work disability due to psoriasis accounted for €1,775 (95% of the indirect costs). Per patient costs of subgroups not receiving systemic therapy (21%), traditional systemic therapy (32%), and biological systemic therapy (47%) amounted to the sum of €1,729, €1,799, and €16,983, respectively. CONCLUSIONS: Patients on biological therapy showed significantly better health related quality of life. As for health economics, the efficacy of systemic treatments is appropriate to be assessed together in patients with moderate to severe psoriasis associated with psoriatic arthritis, since actual health gain might exceed that reported in psoriasis or psoriatic arthritis separately.

Half-life of serum anti-Müllerian hormone and changes after gonadectomy in adult female and male dogs with normal and abnormal gonads.

Anti-Müllerian hormone (AMH) is a biomarker for the presence of gonadal tissue. Changes in serum AMH after gonadectomy are not well established, and its serum half-life is unknown in dogs. We measured serum AMH with a validated electro-chemiluminescent immunoassay in adult female (n = 12) and male (n = 7) dogs with normal gonads, as well as in dogs with gonadal pathology (ovarian remnant syndrome, ORS n = 3, testicular tumor [Leydig cell, Sertoli cell, seminoma] n = 3, unilateral abdominal cryptorchid n = 4) on the day of gonadectomy (D0), and on D3, D7, D14 (females and males), and D21, D28 (males only). Males had higher AMH concentrations than females independent of gonadal status (P < 0.001). Dogs with ORS had lower initial AMH (0.45 ± 0.43 ng/ml) than bitches with normal gonads (1.16 ± 0.44 ng/ml; P = 0.027). Cryptorchid dogs had higher initial concentrations (80.57 ± 52.81 ng/ml) than males with normal gonads (7.92 ± 2.45 ng/ml; P = 0.004), and those with testicular tumors (18.63 ± 5.04 ng/ml) were intermediate (P ≥ 0.250). AMH decreased over time (P ≤ 0.012) and was 0.01-0.04 ng/ml by D14 in females and 0.02-0.12 ng/ml by D28 in males. Serum half-life in the whole study population was 2.85 ± 0.51 days and did not differ between groups. In conclusion, serum AMH can differentiate between intact and gonadectomized status of adult dogs by 14 days after ovario(hyster)ectomy in females and by 28 days after surgical castration in males.

Estimating the healthcare burden of Prurigo Nodularis in England: a CPRD database study.

Purpose: Prurigo nodularis (PN) is a skin disease characterized by intensely itchy skin nodules and is associated with a significant healthcare resource utilization (HCRU). This study aimed to estimate the HCRU of patients in England with PN overall and moderate-to-severe PN (MSPN) in particular.Methods: This retrospective cohort study used data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England. Patients with Mild PN (MiPN) were matched to patients with MSPN by age and gender for the primary analysis. Patients were enrolled in the study between 1st April 2007 and 1st March 2019. All-cause HCRU was calculated, including primary and secondary care contacts and costs (cost-year 2022).Results: Of 23,522 identified patients, 8,933 met the inclusion criteria, with a primary matched cohort of 2,479 PN patients. During follow up, the matched cohort's primary care visits were 21.27 per patient year (PPY) for MSPN group and 11.35 PPY for MiPN group. Any outpatient visits were 10.72 PPY and 4.87 PPY in MSPN and MiPN groups, respectively. Outpatient dermatology visits were 1.96 PPY and 1.14 PPY in MSPN and MiPN groups, respectively.Conclusion: PN, especially MSPN, has a high HCRU burden in England, highlighting the need for new and improved disease management treatments.

Insights into the role of PGF2α in canine periparturient myometrium.

Parturition in dogs is subjected to complex hormonal regulation, with the involvement of prostaglandin F2α (PGF2α) still not fully understood. To investigate uterine inertia (UI), the most prevalent maternal reason for dystocia in the bitch, a better understanding of undisturbed uterine, especially myometrial function, is crucial. Our aim was to gain deeper insights into the role of PGF2α in the canine parturient myometrium. Uterine biopsies were obtained during medically indicated cesarean sections. To test for stimulatory effects of PGF2α in vitro, circular and longitudinal myometrial layer tissue strips were challenged with 50 pM, 0.5 µM, and 50 µM PGF2α. Prostaglandin-endoperoxide synthase 2 (PTGS2) and PGF2α-receptor (PTGFR) mRNA expressions were compared between primary UI (PUI) and obstructive dystocia (OD) samples in isolated parturient myometrium. PTGFR protein expression was assessed in full thickness uterine samples. PGF2α concentrations were analyzed in canine interplacental tissue around term. In the organ bath, the contractile response to PGF2α was limited to the circular layer at the highest dosage. Correspondingly, PTGFR immunohistochemical staining was significantly stronger in the circular layer (p ≤ 0.01). PTGS2 gene expression did not differ between PUI and OD, whereas PTGFR gene expression could not be quantified. Local uterine PGF2α concentrations correlated negatively with serum P4 levels and were the highest during prepartum luteolysis while being significantly lower in PUI. Conclusively, despite the significant increase in local PGF2α concentrations at birth, confirming the interplacental tissue as a production site, our results suggest that PGF2α might affect uterine contractility during labor, mainly indirectly.

The potential clinical impact and cost-effectiveness of the updated COVID-19 mRNA autumn 2024 vaccines in the United Kingdom.

AIMS: To estimate the potential clinical impact and cost-effectiveness of a United Kingdom (UK) Autumn 2024 vaccination campaign with an updated Moderna COVID-19 vaccine in adults ≥65 years and eligible persons 6 months to 64 years of age over a 1-year time horizon (September 2024-August 2025). MATERIALS AND METHODS: A compartmental Susceptible-Exposed-Infected-Recovered model was adapted to reflect COVID-19 cases in the UK. Numbers of symptomatic infections, COVID-19-related hospitalizations and deaths, costs, and quality-adjusted life-years (QALYs) were predicted using a decision tree. The incremental cost-effectiveness ratio (ICER) of an updated Moderna mRNA vaccine (Moderna Autumn 2024 Campaign) was compared to no Autumn 2024 vaccine and to an updated Pfizer-BioNTech mRNA Autumn 2024 vaccine, from a healthcare perspective. RESULTS: The Moderna Autumn 2024 Vaccination Campaign is predicted to decrease the expected 8.3 million symptomatic infections with no vaccination by 19% to 6.7 million. Hospitalizations, long COVID cases, and deaths are expected to decline by 27,000 (-38%), 59,000 (-19%), and 6000 (-43%), respectively. The Moderna Autumn 2024 Campaign will increase QALYs by 78,000 and costs by £665 million, yielding an ICER of £8500/QALY gained. Sensitivity analyses suggest that vaccine effectiveness (VE) and waning, symptomatic infection incidence, hospitalization rates, and mortality rates drive cost-effectiveness. Vaccination remains cost-effective when lowering the target population to ≥50 years. Use of the Moderna vaccine is expected to prevent 8000 more hospitalizations and 1700 more deaths than the updated Pfizer-BioNTech vaccine. CONCLUSIONS: Vaccination of the eligible population would contribute to significant reductions in hospitalizations, deaths, and long COVID in the UK in the 2024-2025 season. Expanding the target population continues to be cost-effective. Use of the Moderna Autumn 2024 Campaign is predicted to reduce SARS-CoV-2 infections and associated outcomes in a cost-effective manner and will contribute to a more resilient healthcare system in the UK.