A comprehensive coding and microRNA transcriptome of vertebral bone in postlarvae and juveniles of Senegalese sole (Solea senegalensis).

Understanding vertebral bone development is essential to prevent skeletal malformations in farmed fish related to genetic and environmental factors. This is an important issue in Solea senegalensis, with special impact of spinal anomalies in postlarval and juvenile stages. Vertebral bone transcriptomics in farmed fish mainly comes from coding genes, and barely on miRNA expression. Here, we used RNA-seq of spinal samples to obtain the first comprehensive coding and miRNA transcriptomic repertoire for postlarval and juvenile vertebral bone, covering different vertebral phenotypes and egg-incubation temperatures related to skeleton health in S. senegalensis. Coding genes, miRNA and pathways regulating bone development and growth were identified. Differential transcriptomic profiles and suggestive mRNA-miRNA interactions were found between postlarvae and juveniles. Bone-related genes and functions were associated with the extracellular matrix, development and regulatory processes, calcium binding, retinol and lipid metabolism or response to stimulus, including those revealed by the miRNA targets related to signaling, cellular and metabolic processes, growth, cell proliferation and biological adhesion. Pathway enrichment associated with fish skeleton were identified when comparing postlarvae and juveniles: growth and bone development functions in postlarvae, while actin cytoskeleton, focal adhesion and proteasome related to bone remodeling in juveniles. The transcriptome data disclosed candidate coding and miRNA gene markers related to bone cell processes, references for functional studies of the anosteocytic bone of S. senegalensis. This study establishes a broad transcriptomic foundation to study healthy and anomalous spines under early thermal conditions across life-stages in S. senegalensis, and for comparative analysis of skeleton homeostasis and pathology in fish and vertebrates.

Ultrasonographic anatomy of the palmar region of the carpus of the dog.

The palmar region of the canine carpus may be injured by traumatic, inflammatory, infectious, neoplastic, and degenerative disorders. The normal ultrasonographic anatomic features of the dorsal region of the canine carpus have been published, however information regarding the palmar region is currently lacking. The aims of this prospective, descriptive, anatomic study were (1) to describe the normal ultrasonographic characteristics of the palmar carpal structures in medium to large-breed dogs, and (2) to establish a standardized ultrasonographic protocol for evaluating them. As in the previously published study, the current study consisted of two phases: (1) identification phase, in which the palmar structures of the carpus were identified ultrasonographically in fifty-four cadaveric specimens and an ultrasonographic protocol to examine them was developed; and (2) descriptive phase, in which the ultrasonographic characteristics of the main palmar structures in twenty-five carpi of thirteen living healthy adult dogs were documented. The tendons of the flexor muscles of the carpus and digits, the superficial and deep parts of the retinaculum flexorum, the carpal canal and the median and ulnar neurovascular structures were ultrasonographically identified and described. Findings from the current study can serve as a reference for evaluating dogs with suspected injury involving the palmar carpal region using ultrasonography.

Correction: González-Rellán et al. Anatomy of the Palmar Region of the Carpus of the Dog. Animals 2022, 12, 1573.

In the original publication [...].

Anatomy of the Palmar Region of the Carpus of the Dog.

The palmar region of the canine carpus is anatomically complex, and the information found in the literature about its anatomy is inconsistent. The aims of this prospective, descriptive, anatomic study were (1) the clarification and (2) the description of the precise anatomic composition of the palmar region of the canine carpus, with special reference to the canalis carpi. For this study, 92 cadaveric specimens were obtained from 46 dogs that had died for reasons unrelated to this study. Of these, 43 medium-to-large-breed dogs were randomly selected for the dissection of transverse slices of the carpus. Samples of the flexor retinaculum and flexor carpi radialis tendon and surrounding tissues were taken for complementary histology. For additional histology of the palmar structures in their anatomical position, three small breed dogs were randomly selected for obtaining transverse slices. The anatomic characteristics of the components of the palmar region of the canine carpus were qualitatively described, with special attention to the following structures: flexor retinaculum, flexor carpi radialis muscle, arteria and vena mediana, nervus medianus, interflexorius muscle, flexor digitorum profundus muscle, canalis carpi, and arteria and nervus ulnaris. The findings from this study provide reference information about the anatomy of the palmar region of the canine carpus.

Ultrasonographic anatomy of the dorsal region of the carpus of the dog.

The dorsal region of the canine carpus is anatomically complex and its normal ultrasonographic characteristics have not been published. The aims of this prospective, descriptive, anatomic study were (a) to describe the normal ultrasonographic appearance of the dorsal carpal structures in medium to large breed dogs, and (b) to describe a standardized protocol for evaluations. The final study, based on the methodology developed in a pilot study performed in twenty-two carpi, comprised two phases: (a) identification phase, in which a correlation between ultrasound and dissection and anatomic slices was performed in forty-eight cadaver carpi and the ultrasonographic protocol was developed; and (b) descriptive phase, in which the ultrasonographic characteristics of the examined structures in 23 carpi of 12 alive adult and healthy dogs were recorded. The tendons of the abductor pollicis longus and the extensor muscles of the carpus and digits, the dorsal ligaments of the carpus - including the medial and lateral collateral ligaments - the extensor retinaculum, a distal radioulnar fibrocartilage and the regional osseous surfaces were ultrasonographically identified and described. Findings from the current study can be used as a reference for ultrasonographic examinations in dogs with injuries or other diseases affecting the dorsal region of the carpus.

Skeletal Anomalies in Senegalese Sole ( Solea senegalensis), an Anosteocytic Boned Flatfish Species.

Skeletal anomalies affect animal welfare and cause important economic problems in aquaculture. Despite the high frequency of skeletal problems in reared Solea senegalensis, there is lack of information regarding the histological features of normal and deformed vertebrae in this flatfish. The aim of this study was to describe the histopathological and radiographical appearance of vertebral body anomalies. Sixty-seven juvenile fish were radiographically examined 104 or 105 days after hatching. Through radiographic images, vertebral segments were selected and processed for histopathological examination from 7 normal and 7 affected fish. Alterations in bone shape and vertebral fusion were the most significant anomalies in the vertebral bodies. These alterations occurred most frequently between the last 3 abdominal vertebrae and the first 10 caudal centra. Radiographically, deformed vertebrae showed flattening of the endplates and narrowing of the intervertebral spaces. The radiographic findings concurred with the histological lesions where affected vertebrae exhibited irregular endplates and changes in trabecular bone. Radiolucent cartilaginous tissue was evident in the endplates of the deformed vertebra and, in some cases, the cartilaginous material extended from the growth zone into the intervertebral space. These changes were likely the primary alterations that led to vertebral fusion. Fused vertebrae were often reshaped and showed a reorganization of the trabeculae. The formation of metaplastic cartilage is frequent in a variety of anomalies affecting teleost species.

Abdominal ultrasonographic findings in dogs naturally infected with babesiosis.

Canine babesiosis is a tick-borne disease with a worldwide distribution that can involve multiple organs and result in a wide variety of clinical manifestations. Our goal was to describe the sonographic changes occurring in 72 dogs naturally infected with babesiosis. Seven healthy Beagle dogs were used as a control group. The most common finding in all dogs was splenomegaly with a diffuse heterogenic parenchyma and generally reduced echogenicity. Diffuse hypoechoic hepatomegaly and bilaterally increased cortical echogenicity of the renal parenchyma were found more frequently in severe uncomplicated and complicated babesiosis groups. Mean renal resistive index and pulsatility index (PI) values were 0.66/1.35, 0.73/1.91, and 0.71/1.73 for mild uncomplicated, severe uncomplicated, and complicated babesiosis groups, respectively. A markedly increased PI for complicated and severe uncomplicated groups correlated with anemia and severity of renal damage. Ultrasonography can be an adjunct for diagnosis and monitoring canine babesiosis and its systemic complications. The detection of diffuse heterogeneous splenomegaly can support the diagnosis of Babesia infection, because of the high prevalence of this lesion in these patients.

Effects of glatiramer acetate on spasticity in previously interferon-beta-treated and treatment-naive patients with relapsing-remitting multiple sclerosis: a prospective, nonrandomized, open-label, uncontrolled, observational pilot study.

BACKGROUND: Treatment with interferon-beta (IFN-beta) has been related to worsening of muscle spasticity in patients with multiple sclerosis (MS). However, there are no specific data on the effects of glatiramer acetate (GA) on spasticity. OBJECTIVE: The aim of the present study was to assess the effects of GA on spasticity in patients with relapsing-remitting MS who had been previously treated with IFN-beta or were treatment naive. METHODS: Two cohorts of MS patients with spasticity who were about to begin treatment with GA at the approved dosage (20 mg/d) were enrolled in the study: patients who were being switched from IFN-beta due to adverse events or lack of efficacy (cohort 1) and patients who were treatment naive (cohort 2). The follow-up periods for cohorts 1 and 2 were 18 and 12 months, respectively. Patients' physical condition was assessed at baseline and at the end of follow-up using the Modified Ashworth Scale (MAS), Penn Spasm Frequency Scale (PSFS), Global Pain Score (GPS), Adductor Tone Rating Scale, Expanded Disability Status Scale (EDSS), and neurophysiologic tests (latency and amplitude of the Hoffmann reflex [H reflex] in the soleus, and ratio of maximum H reflex to maximum motor response [H/M ratio] in the lower limb). The frequency and severity of adverse events were recorded throughout follow-up, and investigators rated the causal relationship to GA (unrelated, unlikely, possibly, or probably). RESULTS: Twenty-eight patients were included in the study, 13 in cohort 1 and 15 in cohort 2. All patients were white. Cohort 1 was 76.9% female, with a mean (SD) age of 39.85 (9.25) years; cohort 2 was 66.7% female, with a mean age of 40.73 (11.52) years. Cohort 1 had significant reductions from baseline to the end of follow-up in mean scores on the MAS for the right hemibody (from 1.85 [0.61] to 1.18 [0.60]; P = 0.002) and left hemibody (from 1.86 [0.55] to 1.27 [0.65]; P = 0.045), PSFS (from 2.00 [0.91] to 0.36 [0.81]; P = 0.002), and GPS (from 47.69 [13.94] to 24.09 [17.15] mm; P = 0.002). The changes from baseline were not significant on the mean Adductor Tone Rating Scale, EDSS, H-reflex latency or amplitude on either side, or lower-limb H/M ratio on either side. Cohort 2 had significant reductions from baseline in H-reflex latency on the left side (from 30.31 [2.44] to 28.75 [2.01]; P = 0.005) and H/M ratio on the right side (from 0.45 [0.15] to 0.35 [0.19]; P = 0.025). There were no significant changes in mean scores on the MAS for either hemibody, PSFS, GPS, Adductor Tone Rating Scale, EDSS, H-reflex latency on the right side, H-reflex amplitude on either side, or lower-limb H/M ratio on the left side. Sixteen patients experienced a total of 28 adverse events. Seven mild adverse events were considered related to GA: local reaction at the injection site (3 patients); headache/migraine, anxiety, and skin reaction (1 patient each); and an unspecified adverse drug reaction (1 patient). Two serious adverse events (pyelonephritis and pyrexia) occurred during the study, neither of them considered related to GA. CONCLUSIONS: In this pilot study in patients with relapsing-remitting MS, GA treatment did not increase spasticity. Furthermore, the results suggest that GA may reduce spasticity in patients previously treated with IFN-beta. These findings support the conduct of large randomized controlled trials of the effects of GA on spasticity.

Localized pleural mesothelioma causing cranial vena cava syndrome in a dog.

A 9-year-old female crossbred dog was presented to the Hospital Universitario Veterinario Rof Codina (Universidad de Santiago de Compostela, Lugo, Spain) for acute onset of severe, progressive swelling of the head, neck, and cranial trunk. Survey radiographs and ultrasonography revealed a large, heterogeneous mass in the cranial mediastinum, compressing or growing into a large blood vessel within the cranial mediastinum and displacing the heart dorsocaudally. At postmortem examination, the mass was diagnosed as a large, localized mesothelioma. Localized mesotheliomas are rare neoplasms in dogs but should be considered as a possible differential diagnosis for cranial vena cava syndrome. The anatomic distribution and clinical features of mesothelioma in the present report are similar to other cases in humans.

[Homocysteine and cognitive impairment in Parkinson's disease]. / Homocisteína y deterioro cognitivo en la enfermedad de Parkinson.

INTRODUCTION: The relationship between homocysteine (Hc) and vascular diseases has been known for more than 30 years. Lately, Hc has also been related to cognitive and motor impairment. In Parkinson's disease (PD), chronic treatment with levodopa could induce higher levels of Hc, and thus may increase risk of cognitive impairment. AIMS: To confirm that PD patients treated with levodopa have higher levels of Hc and to establish a relationship between Hc, folic acid and vitamin B12 levels. Also, we studied a possible link between those variables and cognitive function. PATIENTS AND METHODS: 58 patients with diagnosis of PD were included (45 under treatment with levodopa). Basal levels of Hc, vitamin B12 and folic acid were determined. Forty five patients underwent neuropsychological evaluation. RESULTS: Hc levels were significantly higher in patients taking levodopa and were not related to levodopa dosage or treatment duration. There was a negative correlation between Hc levels and those of vitamin B12 and folic acid in men but we found no such correlation in women. Entacapone was not found to reduce Hc levels. Hc levels were significantly higher in patients with cognitive impairment (9 out of 45 patients). CONCLUSIONS: Our study confirms presence of high levels of Hc in PD patients under treatment with levodopa, more evident in patients with cognitive impairment.

Homocisteína y deterioro cognitivo en la enfermedad de Parkinson / Homocysteine and cognitive impairment in Parkinson’s disease

Introducción. La relación entre homocisteína (Hc) y enfermedades vasculares se conoce desde hace más de 30 años. En los últimos años se ha relacionado también con deterioro cognitivo y motor. En la enfermedad de Parkinson (EP), el tratamiento crónico con levodopa puede inducir un incremento en los niveles de Hc, implicando un riesgo añadido para el deterioro cognitivo. Objetivos. Confirmar la elevación de los niveles de Hc en pacientes con EP tratados con levodopa, su relación con los niveles de vitamina B12 y folato, y si podía existir una relación entre dichas variables y la función cognitiva. Pacientes y métodos. Se incluyeron 58 pacientes diagnosticados de EP (45 en tratamiento con levodopa), se determinaron los niveles basales de Hc, vitamina B12 y folato, y se realizó una evaluación neuropsicológica en 45 de los pacientes. Resultados. El nivel de Hc estaba significativamente más elevado en los pacientes en tratamiento con levodopa, sin relación con la dosis ni el tiempo en tratamiento. Existía una correlación negativa entre los valores de Hc y vitamina B12 y folato en los hombres, que no se observó en las mujeres. Tomar entacapona no redujo los niveles de Hc. El nivel de Hc estaba significativamente más elevado en los pacientes con deterioro cognitivo (9 de los 45 evaluados).Conclusiones. Nuestro estudio confirma la elevación de los niveles de Hc en pacientes con EP en tratamiento con levodopa, y de forma más evidente en los pacientes con deterioro cognitivo (AU)

Introduction. The relationship between homocysteine (Hc) and vascular diseases has been known for more than 30 years. Lately, Hc has also been related to cognitive and motor impairment. In Parkinson’s disease (PD), chronic treatment with levodopa could induce higher levels of Hc, and thus may increase risk of cognitive impairment. Aims. To confirm that PD patients treated with levodopa have higher levels of Hc and to establish a relationship between Hc, folic acid and vitamin B12 levels. Also, we studied a possible link between those variables and cognitive function. Patients and methods. 58 patients with diagnosis of PD were included (45 under treatment with levodopa). Basal levels of Hc, vitamin B12 and folic acid were determined. Forty five patients underwent neuropsychological evaluation. Results. Hc levels were significantly higher in patients taking levodopa and were not related to levodopa dosage or treatment duration. There was a negative correlation between Hc levels and those of vitamin B12 and folic acid in men but we found no such correlation in women. Entacapone was not found to reduce Hc levels. Hc levels were significantly higher in patients with cognitive impairment (9 out of 45 patients). Conclusions. Our study confirms presence of high levels of Hc in PD patients under treatment with levodopa, more evidentin patients with cognitive impairment (AU)

CD20, CD3, and CD40 ligand microclusters segregate three-dimensionally in vivo at B-cell-T-cell immunological synapses after viral immunity in primate brain.

The clearance of virally infected cells from the brain is mediated by T cells that engage antigen-presenting cells to form supramolecular activation clusters at the immunological synapse. However, after clearance, the T cells persist at the infection site and remain activated locally. In the present work the long-term interactions of immune cells in brains of monkeys were imaged in situ 9 months after the viral inoculation. After viral immunity, the persistent infiltration of T cells and B cells was observed at the infection sites. T cells showed evidence of T-cell receptor signaling as a result of contacts with B cells. Three-dimensional analysis of B-cell-T-cell synapses showed clusters of CD3 in T cells and the segregation of CD20 in B cells, involving the recruitment of CD40 ligand at the interface. These results demonstrate that immunological synapses between B cells and T cells forming three-dimensional microclusters occur in vivo in the central nervous system and suggest that these interactions may be involved in the lymphocyte activation after viral immunity at the original infection site.

Sordera como secuela de meningitis por el virus Toscana / Deafness as a sequela of Toscana virus meningitis

No disponible

Increased plasma levels of TNF-alpha but not of IL1-beta in MPTP-treated monkeys one year after the MPTP administration.

The cause of Parkinson's disease remains unknown although some evidence suggests that an inflammatory reaction, mediated by cytokines such as TNF-alpha and IL-1beta, is related with dopaminergic degeneration in the brain. In the present work we measured the plasma levels of TNF-alpha and IL-1beta in parkinsonian monkeys one year after MPTP administration. TNF-alpha levels were seen to have increased in parkinsonian monkeys reflecting the clinical symptoms observed, while IL-1beta levels remained unchanged. These results suggest that TNF-alpha plays a role in sustaining of dopaminergic degeneration in chronic parkinsonism.

Evidence of active microglia in substantia nigra pars compacta of parkinsonian monkeys 1 year after MPTP exposure.

Inflammatory changes have been found in Parkinson's disease, in humans intoxicated with the parkinsonian toxin MPTP, and in animal models of the disease. However, it is still not known whether inflammatory changes are responsible for active nerve cell death or if they have a protective role against neurodegeneration. In this study, we analyzed the glial reaction in the substantia nigra pars compacta (SNpc) and the striatum of monkeys rendered parkinsosian by chronic MPTP injections. At postmortem examination 1 year after the last MPTP injection, the density of astroglial cells and activated microglial cells in the SNpc, but not in the striatum, of MPTP-intoxicated animals was significantly higher than in the two control animals. These data suggest that neurodegeneration was still active despite the absence of the agent triggering cell death and that the glial reaction is associated with long-term neurodegeneration.

Congenital skeletal abnormalities in a tawny owl chick (Strix aluco).

In this case report, we describe a tawny owl chick (Strix aluco) coming from a Wild Fauna Recovery Center with multiple congenital malformations in the limbs. The animal was unable to fly and showed marked malnutrition and poor general appearance. Physical, radiologic, and anatomic examinations showed osseous malformations including dislocation of radius and carpometacarpus with abnormal nonfunctional fixation of ligamentum propatagialis, absence of most parts of the bones of the manus in both wings, and twisted nonfused left tarsometatarsus with marked griphosis of digits. Routine toxicologic and pathologic examinations did not reveal a specific etiology.

Circadian determinations of cortisol, prolactin and melatonin in chronic methyl-phenyl-tetrahydropyridine-treated monkeys.

The aim of this study was to investigate whether prolactin, melatonin and cortisol are altered in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and if so, whether MPTP may alter the availability of these hormones in chronic experimental parkinsonism. Furthermore, vegetative and sleep disorders have been described in both parkinsonian patients and in MPTP chronic monkeys; these may result indirectly from concomitant hormonal variations. Seven adult male cynomolgus monkeys were used for this experiment. Five were treated with systemic doses of intravenous MPTP but not with L-DOPA or dopaminergic agonists. In their 3rd year of parkinsonism, plasma samples were obtained day and night at 3-hour intervals. Sample collection was repeated three times for each animal. Prolactin, melatonin and cortisol concentrations were determined by enzyme immunoassay and compared with samples taken from the control group. Both MPTP-treated monkeys and the control group displayed a similar secretion pattern for the three hormones, except at several specific times when prolactin and melatonin showed significant differences. No changes were found for cortisol. The results suggest a possible alteration of hormonal metabolism in chronic MPTP parkinsonian monkeys.

Parkinson's disease and inflammatory changes.

In 1988 McGeer and colleagues (Neurology 38, 1285-91) observed an activation of the microglia in substantia nigra pars compacta (SNpc) and striatum of brains from patients with Parkinson's disease. In the years that followed several studies performed in the cerebrospinal fluid and during post-mortem analysis in parkinsonian patients revealed increased levels of cytokines, suggesting the activation of a proinflammatory response. Moreover, Langston and his group described the presence of active microglia in the SNpc of three patients who had been exposed to MPTP several years before death. These results suggested that the inflammatory response may increase negative feed-back into the damaged area of the cerebral parenchyma, inducing an imbalance that could perpetuate and/or accelerate neuronal death over a period of years. Similar results have been obtained in parkinsonian monkeys, rats and mice. For these reasons, several groups have treated parkinsonian animals with different anti-inflammatory drugs and obtained promising results. However, it is still not known whether inflammatory changes are responsible for active nerve cell death or whether they play a protective role in neurodegeneration. These changes are putatively related to neuronal loss and suggest that anti-inflammatory treatment for parkinsonian patients could have beneficial effects in the progression of the disease by slowing down the process of neuronal loss.