ATYPICAL PRESENTATION OF CRYPTOCOCCUS NEOFORMANS IN A KOALA (PHASCOLARCTOS CINEREUS): A MAGNETIC RESONANCE IMAGING AND COMPUTED TOMOGRAPHY STUDY.

Cryptococcosis is a worldwide and potentially fatal mycosis documented in wild and captive koalas ( Phascolarctos cinereus ) caused by Cryptococcus neoformans . Though mainly a subclinical disease, when the nasal cavity is affected, epistaxis, mucopurulent nasal discharge, dyspnea, and facial distortion may occur. This report describes a case of cryptococcosis in a koala where unilateral exophthalmos was the only evident clinical sign and magnetic resonance imaging and computed tomography findings are described. Both advanced imaging techniques should be considered as standard and complementary techniques for nasal cavity evaluation in koalas.

A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, a global health issue. Hyperglycemia, in concert with cytokines, activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway to induce inflammation and oxidative stress contributing to renal damage. There is evidence of microRNA-155 (miR-155) involvement in diabetes complications, but the underlying mechanisms are unclear. In this study, gain- and loss-of-function experiments were conducted to investigate the interplay between miR-155-5p and suppressor of cytokine signaling 1 (SOCS1) in the regulation of the JAK/STAT pathway during renal inflammation and DKD. In experimental models of mesangial injury and diabetes, miR-155-5p expression correlated inversely with SOCS1 and positively with albuminuria and expression levels of cytokines and prooxidant genes. In renal cells, miR-155-5p mimic downregulated SOCS1 and promoted STAT1/3 activation, cytokine expression, and cell proliferation and migration. Conversely, both miR-155-5p antagonism and SOCS1 overexpression protected cells from inflammation and hyperglycemia damage. In vivo, SOCS1 gene delivery decreased miR-155-5p and kidney injury in diabetic mice. Moreover, therapeutic inhibition of miR-155-5p suppressed STAT1/3 activation and alleviated albuminuria, mesangial damage, and renal expression of inflammatory and fibrotic genes. In conclusion, modulation of the miR-155/SOCS1 axis protects kidneys against diabetic damage, thus highlighting its potential as therapeutic target for DKD.

Utility of multidetector CT in severe postpartum hemorrhage.

Postpartum hemorrhage is one of the leading causes of maternal mortality worldwide. According to the time when postpartum hemorrhage develops, it is classified as (a) primary, or early, postpartum hemorrhage (within the first 24 hours after delivery) or (b) secondary, or late, postpartum hemorrhage (>24 hours to 6 weeks after delivery). Primary postpartum hemorrhage may be caused by uterine atony (75%-90% of cases), trauma of the lower portion of the genital tract, uterine rupture, uterine inversion, bladder flap hematoma, retention of blood clots or placental fragments, and coagulation disorders. Secondary postpartum hemorrhage may be caused by uterine subinvolution, coagulopathies, and abnormalities of the uterine vasculature. Extrauterine sources of bleeding include rectus sheath hematoma, direct arterial injuries, and the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Severe postpartum hemorrhage is a life-threatening condition that is diagnosed on the basis of the findings from clinical examination, with or without ultrasonography. Computed tomography (CT) and magnetic resonance imaging are useful in the characterization of postpartum hemorrhage when medical treatment fails. Multidetector CT has an important role when intraabdominal bleeding is suspected and can be considered in cases of recurrent bleeding after embolization, as well as for the evaluation of postsurgical complications. A proposed clinical and CT imaging algorithm for postpartum hemorrhage is presented. A multidisciplinary approach to postpartum hemorrhage is essential to optimize the role of diagnostic and interventional radiology in obstetric hemorrhage, to avoid hysterectomy and thus preserve fertility.

Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition.

BACKGROUND: ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. RESULTS: Our results show that both Delta9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. CONCLUSIONS: Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.

Forensic cases of suspected dog and cat abuse in the Community of Madrid (Spain), 2014-2019.

Companion animal abuse is an issue that concerns not only veterinarians and law enforcement agencies but also society in general. Animals that die under suspicious or violent circumstances should be submitted to reference laboratories for a postmortem examination by veterinary forensic pathologists trained to recognize animal abuse. Nevertheless, the low notification rate of such cases in Spain may explain the country's lag in the development of veterinary forensics and the limited information available on animal abuse epidemiology in comparison with other countries. By sharing information among the entities involved in recognizing animal abuse, we can better address these issues, thus improving veterinary forensics in Spain (and elsewhere). In this study, we analysed the cause and manner of death of 96 dog and cat carcasses suspected of animal abuse. These cases were submitted to our diagnostic laboratory for forensic postmortem examination by public agencies and animal protection centres. To our knowledge, this is the first study to focus on the postmortem analysis of forensic cases of suspected dog and cat abuse in Spain. On the basis of gross and histopathological findings, we distinguished between natural and non-natural abuse-related deaths, classifying the latter. We confirmed that most of the dog deaths were related with abuse, though the suspected abuse and the cause of death did not always coincide. In contrast, cause of death was determined to be natural in many of the cat suspected abuse cases. The most frequent non-natural abuse-related cause of death in dogs was blunt force trauma (n=24, 43.64%), followed by firearm injuries (n=10, 18.18%), asphyxia (n=5, 9.09%), heatstroke (n=3, 5.45%), starvation (n=2, 3.64%), bite injury (n=1, 1.82%), and sharp force trauma (n=1, 1.82%). In cats, the most common cause of death was blunt force trauma (n=9, 21.95%), followed by firearm injuries (n=3, 7.32%) and bite injury (n=2, 4.88%). The main goal of our study is to share our results with the scientific community to advance the field of veterinary forensics in Spain, which will lead to more successful prosecutions by law enforcement agencies. Finally, we highlight that veterinarians who can accurately recognize signs of animal abuse may be able to better respond to cases of companion animal cruelty, which in turn, may prevent possible escalation to interpersonal violence.

[Thromboprophylaxis in patients with previous thromboembolic disease who require major orthopedic surgery]. / Profilaxis de la trombosis en pacientes con antecedentes de enfermedad tromboembólica tributarios de cirugía ortopédica mayor.

Postoperative thromboembolic risk depends on both the patient's predisposing factors and on the surgical procedure. Patients with an objective history of venous thromboembolism who require orthopedic surgery are considered to be at very high postoperative risk. However, no specific prophylactic guidelines have been established for this group. Surgeons and patients have to choose between deciding against surgery or accepting a very high possibility of thromboembolic complications. We believe that this group of patients should be treated with an intensive prophylactic protocol combining physical (impulsion foot pump), pharmacological treatment (low molecular weight heparin [LMWH] administered at therapeutic doses from the third postoperative day) and eventually mechanical methods (removable vena caval filter). This intensive prophylactic protocol has been employed in our hospital since 2003, when we initiated an observational, prospective study in 20 patients with a history of venous thromboembolism (VTE) undergoing major pelvic or lower limb orthopedic surgery. Eighteen patients received postoperative physical prophylaxis and 1 month of therapeutic doses of LMWH. Two patients also received mechanical prophylaxis with a removable vena caval filter. Systematic venography and pulmonary scintigraphy performed 1 month after surgery allowed the diagnosis and treatment of one asymptomatic deep venous thrombosis (DVT) and one asymptomatic pulmonary embolism (PE). Moreover, a massive thrombi retained by the removable vena caval filter was detected in another patient. There were no bleeding events leading to reoperation or deaths. Systematic application of our intensive prophylactic protocol for patients with a history of VTE was safe and effective in preventing thromboembolic recurrence after major orthopedic surgery.

First Radiological Study of a Complete Dental Ontogeny Sequence of an Extinct Equid: Implications for Equidae Life History and Taphonomy.

The sequence of cheek teeth mineralization, eruption, and replacement of an extinct horse species is here documented with radiological techniques for the first time thanks to the exceptional preservation of Hipparion sp. mandibles from Cerro de los Batallones (Madrid Basin, Spain). The sequence of dental ontogeny in mammals provides valuable insights about life history traits, such as the pace of growth, and about the mode of formation of fossiliferous assemblages. We have determined that the order of permanent cheek teeth mineralization and eruption of hipparionine horses is m1, m2, (p2, p3), p4, m3. Cheek teeth mineralization timing of hipparionine horses coincides with the one observed in modern equids. In turn, there are differences in the eruption timing of the p4 and m3 between horses belonging to the Anchitheriinae and Hipparionini compared to equids of the Equus genus that might be related to the shorter durability of the deciduous tooth dp4 in anchitheriine and hipparionine horses and, more broadly, to an increased durability of equid teeth through their evolutionary history. Based on the dental eruption sequence, hipparionine horses are slow-growing, long-living mammals. The Hipparion sp. assemblage from Batallones-10 conforms to an attritional model, as individuals more vulnerable to natural mortality predominate.

Venous International Assessment, VIA scale, validated classification procedure for the peripheral venous system.

PURPOSE: VIA scale is a dynamic performance status tool of the peripheral venous system that is divided into five different grades, composed of three parameters: number of observable puncture points; optimal catheter size for cannulation and ease of performing venipuncture and risk of extravasation. METHODS: Prospective single-center, observational, open, non-randomized study divided into two phases. In the first longitudinal phase, we studied the clinical characteristics and the changes in their peripheral venous systems during intravenous chemotherapy for 16 patients (n=16) for an average period of 24 months. In the second transverse phase, we measured the vein's diameter at the selected puncture points with a high-resolution ultrasound and paired this figure with VIA scale. We selected a group of oncology patients (n=52) and a control group (n=56). RESULTS: In the first phase, the level of agreement between the three reviewers was excellent. The second step was to assess the relationship between the measurements obtained with ultrasound and the VIA scale. The vein diameter measurements show a decrease directly related to the assessment of observers in the VIA scale. CONCLUSIONS: The VIA scale is a simple, easy and practical method for classification of the peripheral venous system in terms of vascular access. The practical application of our VIA scale significantly increases the quality of life of patients by increasing the chances of successful venipuncture and cannulation and thus reducing the risk of extravasation and material costs, allowing both an economical and a safe venous assessment tool.

Maternal malnutrition and offspring sex determine juvenile obesity and metabolic disorders in a swine model of leptin resistance.

The present study aimed to determine, in a swine model of leptin resistance, the effects of type and timing of maternal malnutrition on growth patterns, adiposity and metabolic features of the progeny when exposed to an obesogenic diet during their juvenile development and possible concomitant effects of the offspring sex. Thus, four groups were considered. A CONTROL group involved pigs born from sows fed with a diet fulfilling their daily maintenance requirements for pregnancy. The treated groups involved the progeny of females fed with the same diet but fulfilling either 160% or 50% of pregnancy requirements during the entire gestation (OVERFED and UNDERFED, respectively) or 100% of requirements until Day 35 of pregnancy and 50% of such amount from Day 36 onwards (LATE-UNDERFED). OVERFED and UNDERFED offspring were more prone to higher corpulence and fat deposition from early postnatal stages, during breast-feeding; adiposity increased significantly when exposed to obesogenic diets, especially in females. The effects of sex were even more remarkable in LATE-UNDERFED offspring, which had similar corpulence to CONTROL piglets; however, females showed a clear predisposition to obesity. Furthermore, the three groups of pigs with maternal malnutrition showed evidences of metabolic syndrome and, in the case of individuals born from OVERFED sows, even of insulin resistance and the prodrome of type-2 diabetes. These findings support the main role of early nutritional programming in the current rise of obesity and associated diseases in ethnics with leptin resistance.

Massive Rectal Hemorrhage from the Middle Hemorrhoidal Artery after Blunt Perineal Trauma Without Pelvic Fracture.

BACKGROUND: Severe pelvic hemorrhage after blunt trauma without bony fracture has been reported occasionally, and clinical presentation as a delayed massive rectal bleeding is very rare. CASE STUDY: The case of an 86-year-old woman with massive rectal bleeding 12 h after mild blunt perineal trauma is presented. Physical examination revealed an extensive perineal hematoma and a 2-cm laceration in the posterior rectal wall. Pelvic CT scan revealed a large mesorectal hematoma causing extrinsic compression of the rectal lumen. No bony fracture was observed. Selective arteriography was then performed showing hemorrhage resulting from the right middle hemorrhoidal artery, branch of the internal pudendal artery. Transcatheter embolization of coils successfully controlled the bleeding. However, the patient developed a respiratory distress syndrome and renal failure with no response to the treatment and she died 3 days later. CONCLUSION: This report is unique not only for the unusual association of pelvic hemorrhage and rectal injury after blunt trauma without pelvic fracture but also because of the clinical presentation as a massive rectal bleeding. Undoubtedly, the delayed diagnosis and treatment, 12 h after the trauma, contributed to the fatal outcome.

Morphometric analysis of the cranial cavity and caudal cranial fossa in the dog: a computerized tomographic study.

This investigation was initiated to develop a reliable and simple computerized tomography (CT) method for evaluating the morphometry of the cranial cavity (CC) and caudal cranial fossa in the dog. We obtained linear, area, and volume measurements of the entire CC and the caudal fossa compartment in 24 dogs, using transverse and reformatted sagittal and dorsal CT images. The ratios between the CC and the caudal fossa volumes were calculated, as were the ratios between the CC and caudal fossa midsagittal (MS) areas. There were statistically significant correlations between absolute volume data and certain linear measurements, a positive correlation between volume ratio and weight, and significant differences in absolute volume values and volume ratio between males and females. The volume ratio, MS area, and certain linear measurements included in this study can be considered as accurate parameters to evaluate the relative size of the CC to caudal fossa in the dog. Such quantitative measures may be useful in systematically characterizing Chiari-type malformations and other developmental anomalies in the dog.

Profilaxis de la trombosis en pacientes con antecedentes de enfermedad tromboembólica tributarios de cirugía ortopédica mayor / Thromboprophylaxis in patients with previous thromboembolic disease who require major orthopedic surgery

El riesgo tromboembólico postoperatorio depende de factores propios del paciente y del procedimiento quirúrgico. Los pacientes que ya han sufrido un evento tromboembólico y son tributarios de cirugía ortopédica mayor constituyen el grupo de mayor riesgo. Sin embargo, no se han publicado recomendaciones de consenso específicas para este grupo de pacientes. Cirujanos y pacientes deben escoger entre renunciar a la cirugía o asumir una alta probabilidad de que se produzcan complicaciones tromboembólicas. Estos pacientes son tributarios de una profilaxis tromboembólica intensiva combinando medios físicos (bomba de impulsión plantar), farmacológicos (heparina de bajo peso molecular a dosis terapéuticas a partir del tercer día postoperatorio) y, en caso de tromboembolia pulmonar recurrente, además, medios mecánicos (filtro temporal de vena cava). Este protocolo intensivo se emplea en nuestro hospital desde el año 2003, cuando se inició un estudio prospectivo observacional sobre un total de 20 pacientes con antecedentes tromboembólicos tributarios de cirugía ortopédica mayor en la pelvis o las extremidades inferiores. En 18 pacientes la profilaxis tromboembólica consistió en la aplicación de bomba de impulsión venosa plantar y heparina de bajo peso molecular a dosis terapéuticas durante 1 mes en el postoperatorio. En 2 pacientes se indicó además la colocación de filtro temporal en la vena cava inferior. Mediante gammagrafía pulmonar y flebografía sistemáticas un mes después de la cirugía, se han detectado y tratado 1 trombosis venosa profunda y 1 tromboembolia pulmonar asintomáticas. Además, se objetivó un trombo masivo retenido por el filtro de cava en otro paciente. No se han producido reintervenciones por hemorragias ni complicaciones fatales. La aplicación sistemática de nuestro protocolo de profilaxis tromboembólica intensiva a los pacientes con antecedentes trombóticos se ha mostrado efectiva y segura en la prevención de nuevos episodios en relación con cirugía ortopédica de alto riesgo

Postoperative thromboembolic risk depends on both the patient’s predisposing factors and on the surgical procedure. Patients with an objective history of venous thromboembolism who require orthopedic surgery are considered to be at very high postoperative risk. However, no specific prophylactic guidelines have been established for this group. Surgeons and patients have to choose between deciding against surgery or accepting a very high possibility of thromboembolic complications. We believe that this group of patients should betreated with an intensive prophylactic protocol combining physical (impulsion foot pump), pharmacological treatment (low molecular weight heparin [LMWH] administered at therapeutic doses from thethird postoperative day) and eventually mechanical methods (removable vena caval filter). This intensive prophylactic protocol has been employed in our hospital since 2003, when we initiated an observational,prospective study in 20 patients with a history of venous thromboembolism (VTE) undergoing major pelvic or lower limb orthopedic surgery.Eighteen patients received postoperative physical prophylaxis and 1 month of therapeutic doses of LMWH. Two patients also received mechanical prophylaxis with a removable vena caval filter. Systematic venography and pulmonary scintigraphy performed 1 month after surgeryallowed the diagnosis and treatment of one asymptomatic deep venous thrombosis (DVT) and one asymptomatic pulmonary embolism (PE). Moreover, a massive thrombi retained by the removable vena caval filter was detected in another patient. There were no bleedingevents leading to reoperation or deaths. Systematic application of our intensive prophylactic protocol for patients with a history of VTE was safe and effective in preventing thromboembolic recurrence after majororthopedic surgery