Successful treatment of sebaceous adenitis with oclacitinib and low-dose prednisolone in a dog.

Finding an effective and well-tolerated treatment for canine idiopathic sebaceous adenitis (ISA) can be challenging. This case report describes an 8-year-old male Rottweiler with ISA successfully treated with a combination of oclacitinib and low doses of prednisolone.

Encontrar um tratamento eficaz e bem tolerado para a adenite sebácea idiopática (ISA) pode ser desafiador. Este relato descreve o caso de um cão Rottweiler macho de oito anos de idade tratado satisfatoriamente com uma associação de oclacitinib e baixas doses de prednisolona.

Encontrar un tratamiento efectivo y bien tolerado frente a la adenitis sebácea idiopática (ISA) puede ser un reto difícil. Este artículo describe el caso de un perro Rottweiler de ocho años tratado con eficacia con una combinación de oclacitinib y dosis bajas de prednisolona.

Trouver un traitement efficace et bien toléré pour l'adénite sébacée idiopathique canine (ASI) peut s'avérer difficile. Ce rapport clinique décrit le cas d'un Rottweiler mâle de 8 ans atteint d'ASI et traité avec succès par une combinaison d'oclacitinib et de faibles doses de prednisolone.

Framingham score, renal dysfunction, and cardiovascular risk in liver transplant patients.

Cardiovascular (CV) events represent major impediments to the long-term survival of liver transplantation (LT) patients. The aim of this study was to assess whether the Framingham risk score (FRS) at transplantation can predict the development of post-LT cardiovascular events (CVEs). Patients transplanted between 2006 and 2008 were included. Baseline features, CV risk factors, and CVEs occurring after LT (ischemic heart disease, stroke, heart failure, de novo arrhythmias, and peripheral arterial disease) were recorded. In total, 250 patients (69.6% men) with a median age of 56 years (range, 18-68 years) were included. At transplantation, 34.4%, 34.4%, and 33.2% of patients, respectively, had a low, moderate, and high FRS with a median FRS of 14.9 (range, 0.09-30); 14.4% of LT recipients developed at least 1 CVE at a median of 2.619 years (range, 0.006-6.945 years). In the univariate analysis, factors associated with the development of CVEs were the continuous FRS at LT (P = 0.003), age (P = 0.007), creatinine clearance [estimated glomerular filtration rate (eGFR); P = 0.020], and mycophenolate mofetil use at discharge (P = 0.011). In the multivariate analysis, only the eGFR [hazard ratio (HR), 0.98; 95% confidence interval (CI), 0.97-1.00; P = 0.009] and FRS (HR, 1.06; 95% CI, 1.02-1.10; P = 0.002) remained in the model. Moreover, an association was also found between the FRS and overall survival (P = 0.004) with 5-year survival rates of 82.5%, 77.8%, and 61.4% for the low-, moderate-, and high-risk groups, respectively. Continuous FRS, eGFR, and hepatitis C virus infection were independent risk factors for overall mortality. In our series, the FRS and eGFR at LT were able to predict the development of post-LT CVEs and poor outcomes. Liver Transpl 21:812-822, 2015. © 2015 AASLD.

Assessment of the likelihood of hypothyroidism in dogs diagnosed with and treated for hypothyroidism at primary care practices: 102 cases (2016-2021).

BACKGROUND: There is a possibility that an incorrect diagnosis of hypothyroidism could be made in euthyroid dogs, and the prevalence of hypothyroidism in the dog population remains unknown. OBJECTIVES: To retrospectively assess the percentage of dogs diagnosed with, and treated for, hypothyroidism at first opinion practice which are likely to be hypothyroid and require levothyroxine supplementation. ANIMALS: One hundred two client-owned dogs were included in this study. MATERIALS AND METHODS: The computerized databases of 7 first opinion practices were searched to identify dogs treated with levothyroxine supplementation. Three European College of Veterinary Internal Medicine-Companian Animals (ECVIM-CA) diplomates independently assigned 1 of 4 clinical assessments to each case as follows: confirmed or likely hypothyroid, hypothyroidism suspected but not confirmed, hypothyroidism considered unlikely, and no reason to suspect hypothyroidism. They commented as to whether or not they thought levothyroxine supplementation was appropriate. RESULTS: The clinical assessments of "confirmed or likely hypothyroid"; "Hypothyroidism suspected but not confirmed"; "Hypothyroidism considered unlikely"; and "No reason to suspect hypothyroidism" was assigned respectively by Clinician 1 to 38.2%, 5.9%, 3.9%, and 52% of cases, by Clinician 2 to 48%, 22.6%, 22.6%, 6.9% of cases, and by Clinician 3 to 55.9%, 11.8%, 13.7% and 18.6%. Clinician 1, Clinician 2, and Clinician 3 considered levothyroxine supplementation not indicated in 58.8%, 52.9%, and 45.1% of cases, respectively. CONCLUSION: These results support the concern that hypothyroidism might be overly and incorrectly diagnosed in first opinion practice, and that thyroid function testing should be performed only in those dogs with a high pretest probability of the disease.

Skeletal pathologies track body plan evolution in ichthyosaurs.

Changing predator-prey interactions during the Mesozoic Marine Revolution (MMR) profoundly altered the trajectory of marine tetrapod evolution. Here, we assess potential signatures of this landmark transition through the fossil record of skeletal pathologies in ichthyosaurs - iconic marine reptiles that developed increasingly 'fish-like' body plans over time. We surveyed a stratigraphically constrained sample of 200 Middle Triassic ichthyosaur specimens and compared the type, distribution and prevalence of pathologies with an approximately equivalent assemblage of Early Jurassic age. Overall, skeletal pathologies were equally prevalent in these groups, and most often manifested in species >4 m long. However, pathological bones were found to be concentrated in the hind limbs and tail of Triassic ichthyosaurs, whereas the jaws, forelimbs, and ribcage were preferentially affected in Jurassic taxa. We posit that the occurrence of ankylosed zygapophyses in the caudal peak of Triassic ichthyosaurs could represent a functional by-product of their primitive 'eel-like' swimming. Conversely, increased instances of broken ribs in Jurassic ichthyosaurs may infer ramming or tail strike behaviours that characterise morphologically 'fish-like' marine tetrapods, such as modern toothed whales. Different categories of skeletal pathologies thus evidently reflect structural modifications in the ichthyosaur body plan, and indirectly coincide with ecological turnover during the MMR.

Immunoglobulin E-dependent regulation of the CCR3 chemokine receptor by interferon-gamma in atopic asthmatics.

BACKGROUND: The chemokine receptor CCR3 mediates the migration of cells that play an important role in the pathogenesis of asthma to inflammatory foci. Interferon (IFN)-gamma is known to downregulate the expression of some chemokine receptors. Therefore, we decided to analyze the regulation of CCR3 by IFN-gamma in asthmatics and to characterize the dependence of this process on immunoglobulin E (IgE) levels. METHODS: Atopic asthmatics were treated with IFN-gamma or placebo, and the IgE concentration in the blood was measured using an ultra-micro-ELISA for total IgE. Mononuclear cells from patients and controls were isolated by Ficoll-Hypaque gradient and incubated in the absence or presence of IFN-gamma for different periods of time. After incubation, the cells were washed and lysed for RT-PCR analysis, which was performed using a Perkin-Elmer kit. RESULTS: IFN-gamma treatment apparently improved the evaluated clinical variables; however, the differences were not significant compared to the placebo group. We found that IFN-gamma downregulated CCR3 mRNA expression ex vivo and in vivo in those patients with IgE levels higher than 500 IU/ml, whereas IFN-gamma upregulated CCR3 mRNA expression in patients with IgE levels lower than 500 IU/ml. Correspondence between ex vivo and in vivo results was observed using this approach. There was found to be a direct correlation between total serum IgE and CCR3 mRNA expression. CONCLUSIONS: In those asthmatic patients with high levels of IgE, who are thus susceptible to downregulation of CCR3 by IFN-gamma, a significant therapeutic effect with systemic IFN-gamma might be expected.

Palaeoepidemiology in extinct vertebrate populations: factors influencing skeletal health in Jurassic marine reptiles.

Palaeoepidemiological studies related to palaeoecology are rare, but have the potential to provide information regarding ecosystem-level characteristics by measuring individual health. In order to assess factors underlying the prevalence of pathologies in large marine vertebrates, we surveyed ichthyosaurs (Mesozoic marine reptiles) from the Posidonienschiefer Formation (Early Jurassic: Toarcian) of southwestern Germany. This Formation provides a relatively large sample from a geologically and geographically restricted interval, making it ideal for generating baseline data for a palaeoepidemiological survey. We examined the influence of taxon, anatomical region, body size, ontogeny and environmental change, as represented by the early Toarcian Oceanic Anoxic Event, on the prevalence of pathologies, based on a priori ideas of factors influencing population skeletal health. Our results show that the incidence of pathologies is dependent on taxon, with the small-bodied genus Stenopterygius exhibiting fewer skeletal pathologies than other genera. Within Stenopterygius, we detected more pathologies in large adults than in smaller size classes. Stratigraphic horizon, a proxy for palaeoenvironmental change, did not influence the incidence of pathologies in Stenopterygius. The quantification of the occurrence of pathologies within taxa and across guilds is critical to constructing more detailed hypotheses regarding changes in the prevalence of skeletal injury and disease through Earth history.

Pathological survey on Temnodontosaurus from the Early Jurassic of southern Germany.

Paleopathologies document skeletal damage in extinct organisms and can be used to infer the causes of injury, as well as aspects of related biology, ecology and behavior. To date, few studies have been undertaken on Jurassic marine reptiles, while ichthyosaur pathologies in particular have never been systematically evaluated. Here we survey 41 specimens of the apex predator ichthyosaur Temnodontosaurus from the Early Jurassic of southern Germany in order to document the range and absolute frequency of pathologies observed in this taxon as a function of the number of specimens examined. According to our analysis, most observed pathologies in Temnodontosaurus are force-induced traumas with signs of healing, possibly inflicted during aggressive interactions with conspecifics. When the material is preserved, broken ribs are correlated in most of the cases with traumas elsewhere in the skeleton such as cranial injuries. The range of cranial pathologies in Temnodontosaurus is similar to those reported for extinct cetaceans and mosasaurs, which were interpreted as traces of aggressive encounters. Nevertheless, Temnodontosaurus differs from these other marine amniotes in the absence of pathologies in the vertebral column, consistent with the pattern previously documented in ichthyosaurs. We did not detect any instances of avascular necrosis in Temnodontosaurus from southern Germany, which may reflect a shallow diving life style. This study is intended to provide baseline data for the various types of observed pathologies in large ichthyosaurs occupying the 'apex predator' niche, and potentially clarifies aspects of species-specific behavior relative to other ichthyosaurs and marine amniotes.

Studying Closed Hydrodynamic Models of "In Vivo" DNA Perfusion in Pig Liver for Gene Therapy Translation to Humans.

INTRODUCTION: Expressing exogenous genes after naked DNA delivery into hepatocytes might achieve sustained and high expression of human proteins. Tail vein DNA injection is an efficient procedure for gene transfer in murine liver. Hydrodynamic procedures in large animals require organ targeting, and improve with liver vascular exclusion. In the present study, two closed liver hydrofection models employing the human alpha-1-antitrypsin (hAAT) gene are compared to reference standards in order to evaluate their potential clinical interest. MATERIAL AND METHODS: A solution of naked DNA bearing the hAAT gene was retrogradely injected in 7 pig livers using two different closed perfusion procedures: an endovascular catheterization-mediated procedure (n = 3) with infrahepatic inferior vena cava and portal vein blockage; and a surgery-mediated procedure (n = 4) with completely sealed liver. Gene transfer was performed through the suprahepatic inferior cava vein in the endovascular procedure and through the infrahepatic inferior vena cava in the surgical procedure. The efficiency of the procedures was evaluated 14 days after hydrofection by quantifying the hAAT protein copies per cell in tissue and in plasma. For comparison, samples from mice (n = 7) successfully hydrofected with hAAT and healthy human liver segments (n = 4) were evaluated. RESULTS: Gene decoding occurs efficiently using both procedures, with liver vascular arrest improving its efficiency. The surgically closed procedure (sealed organ) reached higher tissue protein levels (4x10^5- copies/cell) than the endovascular procedure, though the levels were lower than in human liver (5x10^6- copies/cell) and hydrofected mouse liver (10^6- copies/cell). However, protein levels in plasma were lower (p<0.001) than the reference standards in all cases. CONCLUSION: Hydrofection of hAAT DNA to "in vivo" isolated pig liver mediates highly efficient gene delivery and protein expression in tissue. Both endovascular and surgically closed models mediate high tissue protein expression. Impairment of protein secretion to plasma is observed and might be species-related. This study reinforces the potential application of closed liver hydrofection for therapeutic purposes, provided protein secretion improves.

Impaired social behavior in children with benign childhood epilepsy with centrotemporal spikes.

The aim of the present study was to assess the emotional and cognitive aspects of social cognition among patients with rolandic epilepsy. A computerized neuropsychological battery was used for cognitive evaluation. Affective and cognitive social cognition were evaluated using two computerized Theory of Mind tasks. Cognitive abilities and social behavior of 15 children, diagnosed with rolandic epilepsy, ages 7 to 13 years were assessed and compared with 15 age- and education-matched healthy controls. Compared with controls, the epileptic patients had lower scores on verbal and visual learning rate parameters and on verbal processing and were significantly impaired on "affective Theory of Mind" tasks but not on "cognitive Theory of Mind" conditions. Our findings raise the possibility that rolandic epilepsy may affect neural networks affecting cognition and mediating social cognition essential for social behavior, thus challenging the benign nature of the condition.

New ophthalmosaurid ichthyosaurs from the European Lower Cretaceous demonstrate extensive ichthyosaur survival across the Jurassic-Cretaceous boundary.

BACKGROUND: Ichthyosauria is a diverse clade of marine amniotes that spanned most of the Mesozoic. Until recently, most authors interpreted the fossil record as showing that three major extinction events affected this group during its history: one during the latest Triassic, one at the Jurassic-Cretaceous boundary (JCB), and one (resulting in total extinction) at the Cenomanian-Turonian boundary. The JCB was believed to eradicate most of the peculiar morphotypes found in the Late Jurassic, in favor of apparently less specialized forms in the Cretaceous. However, the record of ichthyosaurs from the Berriasian-Barremian interval is extremely limited, and the effects of the end-Jurassic extinction event on ichthyosaurs remains poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Based on new material from the Hauterivian of England and Germany and on abundant material from the Cambridge Greensand Formation, we name a new ophthalmosaurid, Acamptonectes densus gen. et sp. nov. This taxon shares numerous features with Ophthalmosaurus, a genus now restricted to the Callovian-Berriasian interval. Our phylogenetic analysis indicates that Ophthalmosauridae diverged early in its history into two markedly distinct clades, Ophthalmosaurinae and Platypterygiinae, both of which cross the JCB and persist to the late Albian at least. To evaluate the effect of the JCB extinction event on ichthyosaurs, we calculated cladogenesis, extinction, and survival rates for each stage of the Oxfordian-Barremian interval, under different scenarios. The extinction rate during the JCB never surpasses the background extinction rate for the Oxfordian-Barremian interval and the JCB records one of the highest survival rates of the interval. CONCLUSIONS/SIGNIFICANCE: There is currently no evidence that ichthyosaurs were affected by the JCB extinction event, in contrast to many other marine groups. Ophthalmosaurid ichthyosaurs remained diverse from their rapid radiation in the Middle Jurassic to their total extinction at the beginning of the Late Cretaceous.

Tau and 14-3-3 of genetic and sporadic Creutzfeldt-Jakob disease patients in Israel.

One of the largest clusters of genetic Creutzfeldt-Jakob disease (gCJD) is found among Jews of Libyan origin in Israel and is linked to the E200K mutation in PRNP (gCJDE200K). The aim of this study was to compare the levels of cerebrospinal fluid (CSF) biomarkers, Tau and 14-3-3 proteins, between gCJDE200K patients, sporadic CJD (sCJD) patients and non-CJD controls in Israel between the years 1996-2006. The levels of Tau and 14-3-3 proteins in CSF were measured by ELISA and immunoblotting, respectively. CSF Tau levels were similar in gCJDE200K and sCJD, both were significantly higher than in controls [1,107 ± 470 pg/ml [33/46 (72%)] of the cases >1,000 pg/ml, 1,280 ± 580 pg/ml [25/30 (83.3%)], and 354 ± 338 pg/ml [17/243 (6.9%)], respectively, p < 0.001]. 14-3-3 was detected in CSF of 41/53 (77%) of each gCJDE200K and sCJD patients tested, but only in 70/417 (16.8%) of controls (p < 0.001). An inverse correlation was found between disease duration and Tau levels in both gCJDE200K and sCJD (r = -0.464 and r = -0.284). No difference was found in Tau or 14-3-3 between the various codon 129 genotypes. We conclude that CSF biomarkers, Tau and 14-3-3, may be used in the diagnosis in both patients' populations, presenting a similar sensitivity yet Tau assay having higher specificity.

Manejo de pacientes con hipoparatiroidismo: Guías clínicas del Servicio de Endocrinología del Instituto Autónomo Hospital Universitario de Los Andes

El hipoparatiroidismo es una enfermedad endocrina poco común que se caracteriza por niveles bajos de calcio sérico, niveles altos de fosfato sérico y niveles inapropiadamente bajos o ausentes de hormona paratiroidea (PTH) en la circulación. La enfermedad puede aparecer como una patología aislada o en asociación con otra patología. Usualmente la enfermedad es de tipo hereditaria, aunque la causa más común en el adulto es el hipoparatiroidismo adquirido postquirúrgico. La mayoría de los pacientes se presentan con síntomas como parestesias, calambres o tetania, pero eventualmente también podría manifestarse como convulsiones, broncoespasmo, laringoespasmo o arritmias cardiacas. Es importante identificar si la hipocalcemia está asociada o no con un nivel sérico ausente o inapropiadamente bajo de PTH (hipoparatiroidismo) o si la hipocalcemia está asociada con el correspondiente aumento compensatorio de dicha hormona. La anamnesis, las características fenotípicas, la evaluación radiológica y el apropiado perfil bioquímico son determinantes para realizar un diagnóstico correcto. La hipocalcemia sintomática puede ser una emergencia médica que requiera la administración aguda vía endovenosa de calcio. La meta terapéutica principal del manejo crónico incluye mantener en un rango aceptable los niveles de calcio sérico, fosforo sérico y la excreción urinaria de calcio en 24 horas.

Hypoparathyroidism is an uncommon endocrine deficiency disease characterized by low serum calcium levels, elevated serum phosphorus levels, and absent or inappropriately low levels of parathyroid hormone (PTH) in the circulation. The disease may appear as an isolated disorder or in association with other organ defects. Usually the disease is identifiable as hereditary, although the most common acquired cause of hypoparathyroidism in adults is postsurgical. Patients with hypoparathyroidism most often present with paresthesia, cramps, or tetany, but the disorder may also manifest acutely with seizures, bronchospasm, laryngospasm, or cardiac rhythm disturbances. The major general distinction to be made is whether the hypocalcemia is associated with an absent or inappropriately low serum PTH concentration (hypoparathyroidism) or whether the hypocalcemia is associated with an appropriate compensatory increase in PTH. The anamnesis, phenotypical features, radiology evaluation and some biochemical profiles are determinant in an appropriate diagnosis. Symptomatic hypocalcemia can be a medical emergency requiring acute intravenous administration of calcium. The primary goals of chronic management include maintaining within an acceptable range the following indexes: serum total calcium, serum phosphorus and 24-h urine calcium excretion.

Immunopathologic study of erythema dyschromicum perstans (ashy dermatosis).

Erythema dyschromicum perstans (EDP) is a pigmentary disease of unknown etiology in which damage to basal cells is thought to be mediated by adhesion molecules. The aim of this study was to characterize the histopathology and immunopathology of EDP. Forty-three patients from Medellín, Colombia, with the diagnosis of EDP were evaluated. Skin biopsy specimens were obtained for histopathology and immunohistochemistry, using monoclonal antibodies directed against the following markers: CD4, CD8, CD56, CD1a, CD68, CLA, HLA-DR, ICAM-1 and LFA-1alpha. A dermal lymphocytic infiltrate was observed in all cases, with a perivascular location in 86%. Other histologic features included melanophages in all specimens, vacuolization of the basement membrane zone (BMZ) 58% and exocytosis of lymphocytes (53.5%). The mean number of total leukocytes was 1510 cells mm-2 of tissue. There was a predominance of CD8+ T lymphocytes in the dermis and HLA-DR+, ICAM-1+ keratinocytes in the epidermis. Exocytosis of cutaneous lymphocyte antigen (CLA)+cells was observed in areas of BMZ damage, suggesting that response to antigenic stimulation may play a role in the development of EDP.