Improving decision‐making in complicated or rare cases—An approach towards Evidence‐based Veterinary Medicine in small animal reproduction

The concepts of Evidence‐based Veterinary Medicine (EBVM) provide a methodological and systematic approach to include the best evidence from research into clinical decision‐making. These concepts include steps as the search and assessment of relevant research findings and consideration of individual aspects. In addition, owners and other persons involved in animal health care should be included in shared decision‐making. Some breeders have good basic knowledge concerning breeding management and characteristics of diseases and concerning advantages and disadvantages of different therapeutic approaches, while others are notable to understand complex medical interrelations or emergency situations. All these aspects need to be addressed when communicating and discussing different diagnostic, prophylactic and therapeutic options. In special fields, such as small animal reproduction, veterinarians often see animals with rare diseases or complex conditions so that an application of standard therapies and well‐established textbook recommendations is not possible. To learn more about cases too rare for successful systematic research, the case collection tool REPROCASES (www.evssar.org/reprocases) is now available. The aim of this project is to gather information from specialists on small animal reproduction in a multicentre approach. If you see rare or not well‐investigated cases such as cystic ovarian diseases, cryptorchidism or others, you are more than welcome to share your findings via the database. Even if this approach cannot completely replace standardized clinical trials, the idea is to gather more information on effects, prognosis, side effects and long‐term fertility for specific conditions

Do concentrations of non‐esterified fatty acids change during gestation and lactation in healthy bitches?

During the gestation and lactation period, the energy demand in pregnant and lactating bitches is elevated. Non‐esterified fatty acids (NEFAs) are utilized either directly from the fed diet or from body fat storage. High NEFA concentration in the blood plasma leads to an increased risk for diseases. Therefore, measuring blood NEFA concentrations may be an indicator for a period of scarcity. The aim of this study is to explore if serum NEFA concentrations in healthy bitches change during gestation and lactation. Healthy pregnant and lactating bitches were sampled on three appointed dates around parturition. NEFA values were examined with a multiparameter clinical chemistry analyser. All statistical analyses were performed using R. Overall, 38 bitches were enrolled in the study. Twenty‐one bitches were sampled on all three appointed dates. The median NEFA concentration antepartum was 0.73 mmol/L (IQR: 0.59, 1.01); during peak lactation, it was 0.57 mmol/L (IQR: 0.44, 0.82); and around weaning, it was 0.58 mmol/L (IQR: 0.46, 0.73). NEFA concentrations rose slightly with litter size in late gestation. Body condition score had no influence on observed NEFA values. We conclude that NEFA concentrations widely remain within reference ranges in well‐fed pregnant and lactating bitches. Nevertheless, they may be a valuable parameter to assess the actual metabolic status of malnourished pregnant and lactating bitches

Triple-decker complexes incorporating three distinct deck architectures

The reactivity of the dilithioplumbole ([Li$_{2}$(thf)$_{2}$(μ,η$^{5}$-L$^{Pb}$)], L$^{Pb}$ = 1,4-bis-tert-butyl-dimethylsilyl-2,3-bis-phenyl-plumbolyl) towards the reactive pnictogen precursors P$_{4}$, pentaphosphaferrocene, and pentaarsaferrocene ([Cp*Fe(η$^{5}$-E$_{5}$)] (Cp* = η$^{5}$-C$_{5}$Me$_{5}$, E = P, As)) is reported. The reaction with P$_{4}$ afforded a phospholyl lithium complex, via lead-phosphorus exchange, while the reactions with [Cp*Fe(η$^{5}$-E$_{5}$)] yielded the first examples of Pb–Fe–Li heterotrimetallic triple-decker polypnictogenides with three different deck motifs

Progesterone Concentrations during Canine Pregnancy

Pregnancy and lactation are amongst the most challenging times of a bitch’s life. Most studies focusing on the endocrinological aspect of pregnancy consider only a small number of animals. The aim of this study was to evaluate progesterone (P4) concentrations in a large number of bitches during early, mid and late pregnancy. In total, 126 bitches of various breeds were recruited following a thorough clinical and gynecological examination during estrus. Blood samples were collected three times (T1–T3) during pregnancy or from non-pregnant dogs in diestrus, and P4 was measured via chemiluminescence. At T1 (11–19 days post-ovulation (dpo)), serum P4 concentrations were 30.23 ± 6.65 ng/mL and 28.45 ± 6.26 ng/mL, at T2 (23–32 dpo) they were 22.73 ± 6.27 ng/mL and 22.59 ± 5.77 ng/mL and at T3 (52–60 dpo) they were 6.68 ± 2.18 ng/mL and 3.17 ± 2.26 ng/mL, in pregnant (n = 98) and non-pregnant (n = 23) dogs respectively. The P4 concentrations differed significantly between pregnant and non-pregnant animals at the last examination (p ≤ 0.001). In the context of hypoluteoidism, the gathered data yielded interesting results. Overall, 28 out of 98 pregnant bitches showed a greater decline (>15 ng/mL) in P4 concentrations from early to mid-pregnancy, and 56 bitches showed P4 concentrations lower than deemed adequate (>20 ng/mL at T1 and T2, >5 ng/mL at T3) according to existing recommendations. Despite not being supplemented with P4, none of those animals suffered from abortion or preterm delivery. Considering that supplementation of P4 can entail considerable risks for the bitch and the puppies, more research on P4 concentration patterns, diagnosis of hypoluteoidism and treatment indications and options is indicated

Teaching small animal reproduction via virtual patients

Virtual patients have become an interesting alternative in medical education. Due to increasing demands regarding theoretical and clinical teaching and to improve an interdisciplinary approach, a new blended learning concept including virtual patients was developed and implemented in the veterinary curriculum of the Freie Universität Berlin. In the presented project, three virtual patients from the field of canine reproduction were developed. They focus on pregnancy diagnosis with suspected luteal insufficiency, pyometra and benign prostatic hyperplasia, respectively. The results of an evaluation by veterinary students of the 7th semester showed a high acceptance of virtual patients in a blended learning reproduction module in the interdisciplinary lectures. Students especially preferred videos, such as video lectures, hands‐on videos and animations as well as a glossary for background information, to successfully and autonomously work on a virtual case. The content covered by the new modules that were developed in the context of this project is part of a spiral curriculum; they will be revised and enhanced during the clinical year

Long-term survival after percutaneous irreversible electroporation of inoperable colorectal liver metastases

Background: For colorectal liver metastases (CRLM) that are not amenable to surgery or thermal ablation, irreversible electroporation (IRE) is a novel local treatment modality and additional option. Methods: This study is a retrospective long-term follow-up of patients with CRLM who underwent IRE as salvage treatment. Results: Of the 24 included patients, 18(75.0%) were male, and the median age was 57 (range: 28-75) years. The mean time elapsed from diagnosis to IRE was 37.9 +/- 37.3 months. Mean overall survival was 26.5 months after IRE (range: 2.5-69.2 months) and 58.1 months after diagnosis (range: 14.8-180.1 months). One-, three-, and five-year survival rates after initial diagnosis were 100.0%, 79.2%, and 41.2%; after IRE, the respective survival rates were 79.1%, 25.0%, and 8.3%. There were no statistically significant differences detected in survival after IRE with respect to gender, age, T- or N-stage at the time of diagnosis, size of metastases subject to IRE, number of hepatic lesions, or time elapsed between IRE and diagnosis. Conclusion: For nonresectable CRLM, long-term survival data emphasize the value of IRE as a new minimally invasive local therapeutic approach in multimodal palliative treatment, which is currently limited to systemic or regional therapies in this setting

Land-to-sea indicators of the Zanclean megaflood

One debated scenario for the termination of the Messinian salinity crisis 5.33 million years ago is cataclysmic refilling of the Mediterranean Sea through the Zanclean megaflood. Here we present a clear line of onshore-to-offshore evidence for this megaflood spilling over a shallow-water marine corridor in south-east Sicily into the nearby subaqueous Noto Canyon: (i) >300 asymmetric and streamlined erosional ridges aligned with the megaflood direction, (ii) poorly-sorted breccia deposited between the Messinian and Lower Zanclean Trubi Formations, (iii) soft-sediment deformation structures and clastic injections in the breccia and underlying units, and (iv) a 20 kilometre wide erosional shelf channel connecting the ridges with Noto Canyon. Numerical modelling results support the modulation of flow velocity and direction by the excavation of the channel and Noto Canyon. Our findings demonstrate that the Messinian salinity crisis was terminated through a cataclysmic flood, which implies pronounced Mediterranean sea-level drawdown prior to the flooding

Extracellular vesicle miRNAs drive aberrant macrophage responses in NSAID-exacerbated respiratory disease.

Extracellular vesicles (EVs) have been implicated in the pathogenesis of asthma, however, how EVs contribute to immune dysfunction and type 2 airway inflammation remains incompletely understood. We aimed to elucidate roles of airway EVs and their miRNA cargo in the pathogenesis of NSAID-exacerbated respiratory disease (N-ERD), a severe type 2 inflammatory condition. EVs were isolated from induced sputum or supernatants of cultured nasal polyp or turbinate tissues of N-ERD patients or healthy controls by size-exclusion chromatography and characterized by particle tracking, electron microscopy and miRNA sequencing. Functional effects of EV miRNAs on gene expression and mediator release by human macrophages or normal human bronchial epithelial cells (NHBEs) were studied by RNA sequencing, LC-MS/MS and multiplex cytokine assays. EVs were highly abundant in secretions from the upper and lower airways of N-ERD patients. N-ERD airway EVs displayed profoundly altered immunostimulatory capacities and miRNA profiles compared to airway EVs of healthy individuals. Airway EVs of N-ERD patients, but not of healthy individuals induced inflammatory cytokine (GM-CSF and IL-8) production by NHBEs. In macrophages, N-ERD airway EVs exhibited an impaired potential to induce cytokine and prostanoid production, while enhancing M2 macrophage activation. Let-7 family miRNAs were highly enriched in sputum EVs from N-ERD patients and mimicked suppressive effects of N-ERD EVs on macrophage activation. Aberrant airway EV miRNA profiles may contribute to immune dysfunction and chronic type 2 inflammation in N-ERD. Let-7 family miRNAs represent targets for correcting aberrant macrophage activation and mediator responses in N-ERD