Origin, genetic structure and evolutionary potential of the natural hybrid Ranunculus circinatus × R. fluitans.

Understanding the genetic variability of hybrids provides information on their current and future evolutionary role. In this paper, we focus on the interspecific hybrid Ranunculus circinatus × R. fluitans that forms spontaneously within the group Ranuculus L. sect. Batrachium DC. (Ranunculaceae Juss.). Genome-wide DNA fingerprinting using amplified fragment length polymorphisms (AFLP) was employed to determine the genetic variation among 36 riverine populations of the hybrid and their parental species. The results demonstrate a strong genetic structure of R. circinatus × R. fluitans within Poland (Central Europe), which is attributed to independent hybridization events, sterility of hybrid individuals, vegetative propagation, and isolation through geographical distance within populations. The hybrid R. circinatus × R. fluitans is a sterile triploid, but, as we have shown in this study, it may participate in subsequent hybridization events, resulting in a ploidy change that can lead to spontaneous fertility recovery. The ability to produce unreduced female gametes of the hybrid R. circinatus × R. fluitans and the parental species R. fluitans is an important evolutionary mechanism in Ranunculus sect. Batrachium that could give rise to new taxa.

Standard clinical computed tomography fails to precisely visualise presence, course and branching points of deep cerebral perforators.

BACKGROUND: Standard computed tomography (CT) images have earned a well-established position in neuroimaging. Despite that, CT is somehow limited by its resolution, which does not enable to distinctively visualise structures smaller than 300 µm in diameter. Perforating arteries, most of which measure 100-400 µm in diameter, supply important subcortical structures (thalamus, basal ganglia, internal capsule). Consequently, pathologies affecting these vessels (e.g. lacunar strokes) can have a devastating clinical outcome. The aim of our study was to assess standard CT's ability to visualise perforators and compare it with microscopic and micro-CT pictures. MATERIALS AND METHODS: We have obtained 6 brainstem and 17 basal ganglia specimens. We infused them with barium sulphate contrast medium administered into either vertebral or internal cerebral artery. After that, the specimens were fixed in formalin and subsequently a series of CT, micro-CT and microscopic examinations were performed. RESULTS: The median number of visualised perforators in brainstem and basal ganglia specimens was 8 and 3, respectively for CT and 18 and 7 for micro-CT (p < 0.05). Standard CT failed to clearly visualise branching points and vessels smaller than 0.25-0.5 mm (1-2 voxels) in diameter. Parallel vessels, like lenticulostriate arteries could not be differentiated in standard CT due to their proximity being smaller that the resolution. CONCLUSIONS: Basing on our results, we infer that CT is a poor modality for imaging of the perforators, presenting both quantitative and qualitative flaws in contrast with micro-CT.

An updated report on the incidence and epidemiological trends of keratinocyte cancers in the United Kingdom 2013-2018.

Introduction: The most common cancers in the UK are keratinocyte cancers (KCs): the combined term for basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Registration of KC is challenging due to high numbers and multiplicity of tumours per person. Methods: We provide an updated report on the descriptive epidemiology of trends in KC incidence for the resident populations of UK countries (England, Northern Ireland, Scotland and Wales) using population-based cancer registry and pathology report data, 2013-18. Results: Substantial increases in cSCC incidence in England, Scotland and Northern Ireland can be detected for the period of 2013-18, and the incidence of cSCC also increased in Wales from 2016 to 2018. In contrast, however, the pattern of annual change in the incidence of BCC across the nations differs. In England, the incidence of BCC declined slightly from 2016 to 2018, however, the overall trend across 2013-18 is not statistically significant. In Scotland, the incidence of BCC shows some variability, declining in 2017 before increasing in 2018, and the overall trend across 2013-18 was also not statistically significant. In Northern Ireland, the incidence of BCC increased significantly over the study period, and in Wales, the incidence of BCC increased from 2016 to 2018. One in five people will develop non-melanoma skin cancers (NMSC) in their lifetime in England. This estimate is much higher than the lifetime risk of melanoma (1 in 36 males and 1 in 47 females born after 1960 in the UK), which further highlights the burden of the disease and importance of early prevention strategies. Conclusions: We highlight how common these tumours are by publishing the first ever lifetime incidence of NMSC. Additionally, the first time reporting of the age standardised incidence of KC in Wales further confirms the scale of the disease burden posed by these cancers in the UK. With approximately one in five people developing NMSC in their lifetime, optimisation of skin cancer prevention, management and research are essential.

Gaussian Processes with Physiologically-Inspired Priors for Physical Arousal Recognition.

While machine learning algorithms are able to detect subtle patterns of interest in data, expert knowledge may contain crucial information that is not easily extracted from a given dataset, especially when the latter is small or noisy. In this paper we investigate the suitability of Gaussian Process Classification (GPC) as an effective model to implement the domain knowledge in an algorithm's training phase. Building on their Bayesian nature, we proceed by injecting problem- specific domain knowledge in the form of an a-priori distribution on the GPC latent function. We do this by extracting handcrafted features from the input data, and correlating them to the logits of the classification problem through fitting a prior function informed by the physiology of the problem. The physiologically-informed prior of the GPC is then updated through the Bayes formula using the available dataset. We apply the methods discussed here to a two-class classification problem associated to a dataset comprising Heart Rate Variability (HRV) and Electrodermal Activity (EDA) signals collected from 26 subjects who were exposed to a physical stressor aimed at altering their autonomic nervous systems dynamics. We provide comparative computational experiments on the selection of appropriate physiologically-inspired GPC prior functions. We find that the recognition of the presence of the physical stressor is significantly enhanced when the physiologically-inspired prior knowledge is injected into the GPC model.

Malignant thymoma - the most common neoplasm in goats.

In the literature the occurrence of thymomas in goats varies from 0.7 to 25%, depending on the study. Therefore the current investigation was carried out to determine the prevalence of thymoma in goats in Poland. Between 2007 and 2018 at the Warsaw Veterinary Faculty 399 goat autopsies and ultrasound examinations of the chest in other 145 goats were performed. Mediastinal tumors were diagnosed during post mortem examination in 2 goats. Additionally, ultrasound examination of the chest revealed a large mass close to the heart in the thoracic cavity in 1 case. This goat was euthanized and an autopsy confirmed a mediastinal tumor. Histopathological examination, with immunohistochemical tests to anti cytokeratin, p63 and p40 confirmed thymomas in all three cases. In our study thymomas were found in 0.5% (95% CI: 0.1% to 1.8%) of examined goats and they represented the most common malignancy in this species.

Reactive seizures in cats: A retrospective study of 64 cases.

Epileptic seizures are a common indication for neurological evaluation. This retrospective study reviewed 789 cats referred for epileptic seizure evaluation to the Department of Small Animal Medicine and Surgery of the University of Veterinary Medicine in Hannover, between 1998 and 2017. The aim of this study was to determine common causes for reactive seizures (RS) in cats. Reactive seizures were diagnosed in 62 (7.9%) of 789 feline patients. The most common cause of RS was presumptive or confirmed intoxication (n=34/62; 54.8%). Toxins included permethrin (n=5/62; 8.1%), fipronil (n=1/62; 1.6%), and pesticide (n=1/62; 1.6%). Other common causes were hepatic and renal encephalopathy (n=6/62; 9.7% each), hypertension (n=5/62; 8.1%), hyperthyroidism (n=3/62; 4.8%), hypoglycaemia (n=3/62; 4.8%), and hyperglycaemia (n=1/62; 1.6%). Most commonly, cats with RS presented with generalised tonic-clonic seizures (n=25/62; 40.3%). A single status epilepticus was observed in 9.7% (n=6/62) and 4.8% (n=3/62) presented only with cluster seizures. Focal seizures were the only presenting sign in 3.2% (n=2/62) of cases, however in 4.8% (n=3/62) they were accompanied by tonic-clonic seizures. The mean age of all cats presented for RS was 10.8 years. In the intoxication group, the mean age was 2.9 years. Intoxication (confirmed or presumptive) was the most common cause of RS identified. Clinicians should suspect intoxication when other causes of RS are excluded; when there are appropriate historical findings; when the cat is frequently unobserved by the owner; when symptomatic treatment leads to cessation of epileptic seizures; and when seizures do not recur after treatment has been discontinued.

Dega pelvic osteotomy: indications, results and complications.

PURPOSE: Developmental dysplasia of the hip (DDH) after walking age is difficult to treat. Dega pelvic osteotomy is combined with open reduction and femoral osteotomy to obtain concentric stable reduction with good coverage of the femoral head. The purpose of this study is to evaluate the use of the Dega osteotomy in the treatment of DDH in two different age groups. METHODS: A total of 45 patients (52 hips) with a mean age of 3.9 years (1.2 to 12.8) were treated with open reduction, Dega osteotomy and femoral osteotomy. There were 38 dislocated and 14 subluxated hips. Bilateral DDH was observed in seven female patients. Radiographic parameters included acetabular index, centre-edge angle of Wiberg and migration percentage. The final radiographic outcome was evaluated according to the Severin classification. RESULTS: The mean follow-up period was four years (3 to 9). According to the Severin criteria 78.8% were types I or II whereas 21.2% showed types III or IV. There was no statistically significant difference in final outcome between children less than three years of age and older children at the time of surgery.One hip in children with unilateral involvement had developed coxa magna, that interfered with hip concentricity. Three hips (5.8%) showed avascular necrosis of the femoral head. CONCLUSION: Dega osteotomy is a safe and adequate procedure for the management of developmental dysplasia of the hip in walking patients with low complication rates. Restoring the acetabulum to normal or nearly normal can result in good medium-term results. LEVEL OF EVIDENCE: III.

Clinical Risk Factors for Early Seizure Recurrence in Dogs Hospitalized for Seizure Evaluation.

BACKGROUND: Epileptic seizures are a common cause for neurological evaluations in dogs. HYPOTHESIS/OBJECTIVES: To determine the timing, frequency, and risk factors for early seizure recurrence (ESR) among dogs admitted to the hospital for seizure evaluation and to facilitate rapid decision making about whether dogs should be placed in the intensive care unit (ICU) or day ward. ANIMALS: Nine-hundred twenty-two dogs referred for seizure investigation; 214 patients were included. METHODS: Retrospective study. Medical records between 2000 and 2017 were reviewed to determine risk factors for ESR. Findings were compared among dogs diagnosed with idiopathic epilepsy (IE), structural epilepsy (StE) and reactive seizures (RS), as well as in all selected cases together. RESULTS: Fifty percent of dogs had a seizure while hospitalized. In the group 53.1 and 52.2% in the StE group, whereas in the RS 40.44% had ESR. The average time to ESR was 7 hours. In IE group, abnormal postictal neurological examination with prosencephalon signs predicted ESR. In StE group, a single generalized or focal seizure 72 hours before hospital admission and abnormal neurologic examination predicted ESR. In the RS group, ERS was predicted by long-term antiepileptic monotheraphy. When all dogs were analyzed together, abnormal neurological examination, the occurrence of cluster seizures, status epilepticus, or combination of them 72 hours before presentation predicted ESR. CONCLUSIONS AND CLINICAL IMPORTANCE: Epileptic seizures recurred in 50% of patients within a mean time of 7 hours. In general, when cluster seizures, status epilepticus or both occurred 72 hours before presentation and neurological examination was abnormal upon presentation, the dog should be placed in ICU for observation.

The expression pattern and inhibitory influence of Tenascin-C on the growth of spiral ganglion neurons suggest a regulatory role as boundary formation molecule in the postnatal mouse inner ear.

Sensorineural hearing loss, as a consequence of acoustic trauma, aging, genetic defects or ototoxic drugs, is highly associated with irreversible damage of cochlear hair cells (HCs) and secondary degeneration of spiral ganglion (SG) cells. Cochlear implants (CIs), which bypass the lost HC function by direct electrical stimulation of the remaining auditory neurons, offer an effective therapy option. Several studies imply that components of the extracellular matrix (ECM) have a great impact on the adhesion and growth of spiral ganglion neurons (SGNs) during development. Based on these findings, ECM proteins might act as bioactive CI substrates to optimize the electrode-nerve interface and to improve efficacy of these implants. In the present study, we focused on the ECM glycoproteins Tenascin-C (TN-C), Laminin (LN), and Fibronectin (FN), which show a prominent expression along the growth route of SGNs and the niche around HCs during murine postnatal development in vivo. We compared their influence on adhesion, neurite length, and neurite number of SGNs in vitro. Moreover, we studied the expression of the chondroitin sulfate proteoglycan (CSPG) dermatan sulfate-dependent proteoglycan-1 (DSD-1-PG), an interaction partner of TN-C. In sum, our in vitro data suggest that TN-C acts as an anti-adhesive and inhibitory factor for the growth of SGNs. The DSD-1 carbohydrate epitope is specifically localized to HC stereocilia and SG fibers. Interestingly, TN-C and the DSD-1-PG exhibit a mutually exclusive expression pattern, with the exception of a very restricted region beneath the habenula perforata, where SG neurites grow through the basilar membrane (BM) toward the HCs. The complementary expression of TN-C, LN, FN, and the DSD-1 epitope suggests that TN-C may act as an important boundary formation molecule in the developing postnatal mouse inner ear, which makes it a promising candidate to regulate neurite outgrowth in the light of CIs.

Evaluation of the effect of 2,4-dichlorophenol on oxidative parameters and viability of human blood mononuclear cells (in vitro).

2,4-Dichlorophenol (2,4-DCP) is formed in drinking water as a result of its chlorination, and it is created in the environment during transformation of various xenobiotics such as triclosan or herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). The molecular mechanism depicting the action of phenolic compounds on nucleated blood cells has been insufficiently studied, and therefore, we have assessed the effect of 2,4-DCP on the structure and viability of human peripheral blood mononuclear cells (PBMCs). We have evaluated necrotic, apoptotic, and morphological changes (alterations in the size and granulation) in PBMCs incubated with 2,4-DCP in the concentration ranging from 10 to 500 µg mL(-1) for 4 h at 37°C. Moreover, we have estimated changes in reactive oxygen species (ROS) formation, lipid peroxidation, and protein carbonylation in the incubated cells. We have noted that 2,4-DCP increased ROS formation and lipid peroxidation (from 10 µg mL(-1)) and oxidized proteins (from 50 µg mL(-1)) in PBMCs. The compound studied also provoked apoptotic (from 50 µg mL(-1)), necrotic (from 100 µg mL(-1)) and alterations in the size and granulation (from 50 µg mL(-1)) in the incubated cells. The analysis of quinolinium 4-[(3-methyl-2(3H)-benzoxazolylidene)methyl]-1-[3-(trimethyl-ammonio)-propyl]-diiodide/propidium iodide staining revealed that 2,4-DCP (50-250 µg mL(-1)) more strongly increased the number of apoptotic than necrotic cells, which suggests that this cell death type is mainly provoked by this compound in PBMCs. The observed changes were caused by relatively high concentrations of 2,4-DCP, which cannot influence human organism during environmental exposure and thus may only occur as a result of acute or subacute poisoning with this compound.

The impact of demographic, social, and environmental factors on the development of steroid-responsive meningitis-arteritis (SRMA) in the United Kingdom.

BACKGROUND: Steroid-responsive meningitis-arteritis (SRMA) is an inflammatory disease of dogs that is suspected to be immune-mediated. The development of other immune-mediated diseases has been linked to vaccinations, time of the year, geographic location, sex, neuter status, and breed. HYPOTHESIS/OBJECTIVES: To identify if the development of SRMA is associated with time of year, vaccination, geographic location, sex, neuter status, and breed. ANIMALS: Sixty SRMA cases and 180 controls, all ≤24 months of age and matched for year of presentation, from a referral hospital population in the United Kingdom. METHODS: Retrospective case-control study with unconditional logistic regression analysis. RESULTS: Beagles (P = .001), Border Collies (P = .001), Boxers (P = .032), Jack Russell Terriers (P = .001), Weimaraners (P = .048), and Whippets (P < .001) had significantly greater odds of developing SRMA in this population of dogs. Vaccination, time of year, geographic category, sex, and neuter status did not increase the odds of developing SRMA. CONCLUSIONS AND CLINICAL IMPORTANCE: Only breed increased the odds of developing SRMA. It would be prudent to investigate the genetics of the identified breeds to help elucidate the etiopathogenesis of SRMA.

Can palmar creases serve as landmarks for the deeper neuro-vascular structures?

PURPOSE: The aim of this study was the examination of the superficial anatomy of palmar creases and their relation to deeper neuro-vascular structures. METHODS: Four creases: distal wrist flexion crease, thenar crease, proximal palmar crease and distal palmar crease were evaluated with reference to the following structures: palmar cutaneous branch of median nerve, palmar cutaneous branch of ulnar nerve, the nerve of Henle, transverse palmar branches from ulnar nerve, recurrent motor branch of median nerve, radial proper palmar digital nerve to the index and the ulnar proper palmar digital nerve to the thumb, Berrettini's communicating branch, ulnar nerve and artery, superficial palmar arch. We performed dissections of 20 cadaveric upper limbs derived from a homogenous Caucasian group. In our study we measured the location of surgically important structures with reference to palmar skin creases. RESULTS: Among the other observations we noticed that the palmar cutaneous branches of the median and ulnar nerves were located at least 0.5 cm away from the thenar crease. The superficial palmar arch was found between the thenar and proximal palmar crease and never crossed the proximal or distal palmar creases. CONCLUSIONS: These anatomical dissections will provide reference material for further ultrasound studies on the arrangements of neuro-vascular structures in reference to superficial palmar creases.

Electroencephalography recording analysis in monitoring of canine idiopathic epilepsy treated with phenobarbital. Pilot study.

EEG recording is used in veterinary medicine as a diagnostic tool to support clinical diagnosis of idiopathic epilepsy and to identify focal seizure activity. This retrospective study was designed to compare EEG procedures in 23 dogs with idiopathic epilepsy before and after phenobarbital treatment. Differences among standard deviations for particular bands were significant. During phenobarbital treatment the delta band decreased.

A comparison of magnetic resonance imaging sequences in evaluating pathological changes in the canine spinal cord.

This paper discusses 28 canine patients subjected to low-field magnetic resonance imaging (MRI) of the spinal cord for neurological indications. The authors describe and compare the used MRI sequences with an indication of the most effective sequences in MRI examinations that require short scanning time. The most effective sequences supporting a quick diagnosis of spinal diseases in dogs were SE (spin echo), FSE (fast spin echo) and 3D HYCE (hybrid contrast enhancement).

Magnetic resonance imaging of selected limb joints in dogs.

The presented paper presents updated information concerning magnetic resonance imaging (MRI) of shoulder joint, elbow joint and knee joint in dogs. It describes indications, planes, standard sequences, slice thickness to perform MRI examination of above mentioned joints. Besides general information about basic physics use in magnetic resonance imaging, and practical information about magnetic resonance and it usage in orthopedic examination are given.

The FAAH inhibitor URB-597 interferes with cisplatin- and nicotine-induced vomiting in the Suncus murinus (house musk shrew).

Considerable evidence implicates the endocannabinoid system as a neuromodulator of nausea and vomiting. The action of anandamide (AEA) can be prolonged by inhibiting its degradation, through the use of URB597 (URB), a Fatty Acid Amide Hydrolase (FAAH) enzyme inhibitor. Here we present evidence that the FAAH inhibitor, URB, interferes with cisplatin- and nicotine-induced vomiting in the Suncus murinus. In Experiment 1, shrews were injected with URB (0.9 mg/kg) or vehicle 120 min prior to the behavioral testing. They received a second injection of AEA (5 mg/kg) or vehicle 15 min prior to being injected with cisplatin (20 mg/kg) or saline and the number of vomiting episodes were counted for 60 min. In Experiment 2, shrews were injected with vehicle or URB (0.9 mg/kg) 120 min prior to receiving an injection of nicotine (5 mg/kg) or saline and the number of vomiting episodes were counted for 15 min. Experiment 3 evaluated the potential of the CB(1) antagonist, SR141716, to reverse the effect of URB on nicotine-induced vomiting. URB attenuated vomiting produced by cisplatin and nicotine and the combination of URB+AEA suppressed vomiting produced by cisplatin. The effect of URB on nicotine-induced vomiting was reversed by SR141716. These data suggest that the EC system plays a tonic role in the regulation of toxin-induced vomiting.

A mass action model of a Fibroblast Growth Factor signaling pathway and its simplification.

We consider a kinetic law of mass action model for Fibroblast Growth Factor (FGF) signaling, focusing on the induction of the RAS-MAP kinase pathway via GRB2 binding. Our biologically simple model suffers a combinatorial explosion in the number of differential equations required to simulate the system. In addition to numerically solving the full model, we show that it can be accurately simplified. This requires combining matched asymptotics, the quasi-steady state hypothesis, and the fact subsets of the equations decouple asymptotically. Both the full and simplified models reproduce the qualitative dynamics observed experimentally and in previous stochastic models. The simplified model also elucidates both the qualitative features of GRB2 binding and the complex relationship between SHP2 levels, the rate SHP2 induces dephosphorylation and levels of bound GRB2. In addition to providing insight into the important and redundant features of FGF signaling, such work further highlights the usefulness of numerous simplification techniques in the study of mass action models of signal transduction, as also illustrated recently by Borisov and co-workers (Borisov et al. in Biophys. J. 89, 951-966, 2005, Biosystems 83, 152-166, 2006; Kiyatkin et al. in J. Biol. Chem. 281, 19925-19938, 2006). These developments will facilitate the construction of tractable models of FGF signaling, incorporating further biological realism, such as spatial effects or realistic binding stoichiometries, despite a more severe combinatorial explosion associated with the latter.

Phosphorylation of H2AX histone as indirect evidence for double-stranded DNA breaks related to the exchange of nuclear proteins and chromatin remodeling in Chara vulgaris spermiogenesis.

Phosphorylation of H2AX histone results not only from DNA damage (caused by ionizing radiation, UV or chemical substances, e.g. hydroxyurea), but also regularly takes place during spermiogenesis, enabling correct chromatin remodeling. Immunocytochemical analysis using antibodies against H2AX histone phosphorylated at serine 139 indirectly revealed endogenous double-stranded DNA breaks in Chara vulgaris spermatids in mid-spermiogenesis (stages V, VI and VII), when protamine-type proteins appear in the nucleus. Fluorescent foci were not observed in early (stages I-IV) and late (VIII-X) spermiogenesis, after replacement of histones by protamine-type proteins was finished. A similar phenomenon exists in animals. Determination of the localization of fluorescent foci and the ultrastructure of nuclei led to the hypothesis that DNA breaks at stage V, when condensed chromatin adheres to the nuclear envelope. This is transformed into a net-like structure during stage VI, probably allowing chromosome repositioning to specific regions in the mature spermatozoid. However, at stages VI and VII, DNA breaks are necessary for transformation of the nucleosomal structure into a fibrillar and finally the extremely condensed status of sleeping genes at stage X.