MULTIDETECTOR COMPUTED TOMOGRAPHIC AND LOW-FIELD MAGNETIC RESONANCE IMAGING ANATOMY OF THE QUADRIGEMINAL CISTERN AND CHARACTERIZATION OF SUPRACOLLICULAR FLUID ACCUMULATIONS IN DOGS.

Focal fluid accumulations in the supracollicular region are commonly termed quadrigeminal cysts and may be either subclinical or associated with neurologic deficits in dogs. Little published information is available on normal imaging anatomy and anatomic relationships for the canine quadrigeminal cistern. Objectives of this observational, cross-sectional study were to describe normal quadrigeminal cistern anatomy and determine the prevalence and characteristics of supracollicular fluid accumulations in dogs. Normal descriptions were accomplished using computed tomographic (CT) cisternography in one canine cadaver, and CT and magnetic resonance imaging (MRI) studies of the brain in four prospectively recruited dogs with no evidence of intracranial disease. Prevalence and characteristics descriptions were accomplished using a retrospective review of brain CT or MRI studies performed during the period of 2005-2015. The normal quadrigeminal cistern consistently exhibited a complex H shape and was separated from the third ventricle by a thin membrane. Prevalence of supracollicular fluid accumulations (SFAs) was 2.19% among CT studies (n = 4427) and 2.2% among MRI studies (n = 626). Dogs with SFA were significantly younger than control dogs (P < 0.0001). Shih-tzu (OR = 111.6), Chihuahua (OR = 81.1), and Maltese (OR = 27.6) breed dogs were predisposed (P < 0.0001). Among dogs with SFAs, the following three patterns were defined: (1) third ventricle (49.54%), (2) quadrigeminal cistern (13.51%), and (3) both third ventricle and quadrigeminal cistern (36.93%). Authors recommend that the term supracollicular fluid accumulation (SFA) should be used rather than the term quadrigeminal cyst to describe these focal fluid accumulations in dogs.

Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) has a central role in cancer progression and metastatic dissemination and may be induced by local inflammation. We asked whether the inflammation-induced acquisition of mesenchymal phenotype by neoplastic epithelial cells is associated with the onset of mesenchymal stromal cell-like immune-regulatory properties that may enhance tumour immune escape. METHODS: Cell lines of lung adenocarcinoma (A549), breast cancer (MCF7) and hepatocellular carcinoma (HepG2) were co-cultured with T, B and NK cells before and after EMT induction by either the supernatant of mixed-lymphocyte reactions or inflammatory cytokines. RESULTS: EMT occurrence following inflammatory priming elicited multiple immune-regulatory effects in cancer cells resulting in NK and T-cell apoptosis, inhibition of lymphocyte proliferation and stimulation of regulatory T and B cells. Indoleamine 2,3-dioxygenase, but not Fas ligand pathway, was involved at least in part in these effects, as shown by the use of specific inhibitors. CONCLUSIONS: EMT induced by inflammatory stimuli confers to cancer cells some mesenchymal stromal cell-like immune-modulatory properties, which could be a cue for cancer progression and metastatic dissemination by favouring immune escape.

Acquired partial lower urinary tract obstruction caused by intravesical ureterocele in an adult dog.

Ureterocele is an uncommon condition in dogs characterised by a cystic dilation of the submucosal portion of the distal ureter. A 4-year-old intact male Siberian husky with a 4-month previous diagnosis of ureterocele was presented for pollakiuria. Abdominal ultrasound showed increased dimensions of the ureterocele, and a retrograde positive contrast urethrocystography detected a filling defect of the bladder neck lumen. The position of ureterocele was considered responsible for the partial urinary obstruction. This hypothesis is supported by the resolution of pollakiuria after surgical ureterocele resection. Based on a literature search, this is the first case of an intravesical ureterocele causing partial urinary obstruction in dogs. Ureterocele should be considered as a differential diagnosis in patients with pollakiuria.

Effects of a single mannitol bolus on cerebral hemodynamics in intracerebral hemorrhage: a transcranial Doppler study.

BACKGROUND: Mannitol infusion is widely used in clinical practice to reduce perilesional edema in intracerebral hemorrhage (ICH), though no controlled studies have yet provided evidence of its effects on clinical outcome or on cerebral blood flow impairment following the event. The aim of our study was to evaluate blood flow velocity changes in the middle cerebral arteries (MCA) after a mannitol bolus in patients with ICH. METHODS: Transcranial Doppler bilateral monitoring was performed for 90 min in 20 patients with ICH, during 100 ml mannitol bolus i.v. administration. The MCA mean flow velocities (MFVs) and pulsatility index (PI) were recorded. RESULTS: When the 'healthy' and the 'affected' hemispheres were compared, we observed higher MCA MFV and lower PI on the affected side than on the contralateral side, both at baseline and during the experiment. After the mannitol bolus, we observed a significant MFV increase, starting at the end of the infusion and lasting longer than 60 min in the MCA on the affected side alone. The PI increased after mannitol administration on the healthy side alone. CONCLUSIONS: A single bolus of mannitol modified cerebral hemodynamics in our patients with ICH, increasing flow velocities on the affected MCA. This effect may be a consequence of reduced edema in the perilesional areas. The increased PI on the unaffected side may be indicative of preserved pulsatility in the healthy hemisphere.

Advantages and pitfalls of three-dimensional ultrasound imaging of carotid bifurcation.

OBJECTIVES: Several specialists use three-dimensional (3D) ultrasound as adjuvant imaging technique in their clinical practice. It has been applied to study carotid plaque morphology, surface and volume during atherosclerosis progression. Nonetheless, no papers have so far described the use of this technique in conditions different than carotid stenosis, such as bifurcation anatomy changes of the caliber and vessel course modifications. METHODS: Patients admitted to our ultrasound laboratory for vascular screening were submitted to standard carotid duplex and to 3D ultrasound reconstruction of the carotid bifurcation. RESULTS: Forty normal subjects, 7 patients with caliber alterations (4 carotid bulb ectasia and 3 internal carotid lumen narrowing), 45 patients with course variations (tortuosities and kinking) and 35 patients with internal carotid artery stenosis of various degrees have been investigated. CONCLUSIONS: 3D ultrasound is a feasible technique. It can improve carotid axis imaging through a better presentation of caliber variations and vessel course 'at a glance'. 3D ultrasound from the inward flow can provide imaging of the stenosis, but stenosis quantification should always take into account the assessment of plaque morphology and vessel wall.

Transcranial Doppler for brain death in infants: the role of the fontanelles.

OBJECTIVE: Transcranial Doppler (TCD) is a sensitive technique for circulatory arrest diagnosis in brain death when patterns such as reverberant flow and short systolic spikes are observed. In infants, the nonossified fontanelles compensate for intracranial hypertension. We describe TCD patterns in infants with brain death, different from adults, with the hemodynamic modifications induced by anterior fontanelle compression. METHOD: TCD was performed in 2 infants with diagnosed brain death admitted to the neonatal intensive care unit. RESULTS: TCD showed a large peak 'reverberant' flow, with a high peak systolic velocity and a consistent retrograde component, away from the brain. Compression of the anterior fontanelle induced, at first, a reduction in systolic flow with the subsequent appearance of the characteristic short systolic spikes. Upon compression removal, a brief increase in the systolic flow was observed before the prompt reappearance of the reverberant flow. CONCLUSION: TCD for brain death diagnosis should be done cautiously in infants. In these cases, reverberating flow may be indicative of circulatory arrest even if with a large peak and with a high peak systolic velocity. Heavy fontanelle compression may reproduce the classical adult TCD patterns of brain death, thus supporting the diagnosis of cerebral circulatory arrest.

Contrast carotid ultrasound for the detection of unstable plaques with neoangiogenesis: a pilot study.

OBJECTIVES: To evaluate whether contrast ultrasonography can be used to distinguish asymptomatic from symptomatic carotid plaques and provide insight into underlying pathophysiological differences. DESIGN: Contrast carotid ultrasound was performed in both symptomatic and asymptomatic patients referred for carotid endarterectomy. MATERIALS AND METHODS: Of 77 consecutive patients referred for carotid artery evaluation, 64 underwent carotid endarterectomy for asymptomatic cerebrovascular disease and 9 underwent urgent surgery for acute neurological deficits with hemiparesis. The endarterectomy specimens were assessed immunohistologically. RESULTS: In all 9 patients undergoing urgent surgery, contrast ultrasonography showed the accumulation of diffuse microbubble contrast at the base of the carotid plaque. This pattern was observed only in 1/64 of the patients undergoing surgery for asymptomatic carotid disease. Immunohistologically staining of the endarterectomy specimens showed that the area of microbubble contrast at the base of the symptomatic plaques was associated with an increased number of small diameter (20-30 microm) microvessels staining for vascular endothelial growth factor (VEGF). CONCLUSIONS: Contrast carotid ultrasonography may allow the identification of microvessels with neoangiogenesis at the base of carotid plaques, and differentiate symptomatic from asymptomatic plaques.

Smoking E-CigaRette and HEat-noT-burn products: validation of the SECRHET questionnaire.

BACKGROUND: The nicotine market has rapidly evolved with the emergence of newer forms of smoking device that have been expanded worldwide, such as electronic cigarettes (eCig) which heat a solution (e-liquid) to create vapour and heat-not-burn (HNB) tobacco products, which heats tobacco at a temperature below the point of combustion. Their use is increasing at an alarming rate; it is believed it will surpass the use of traditional cigarettes in next 5 years, mostly among never-smokers and young people. OBJECTIVE: There are not many studies investigating knowledge and behaviour about heat tobacco products (HTP) among teenagers, so the aim of this study is to validate the SECRHET questionnaire (Smoking E-CigaRette and HEat-noT-burn products) on knowledge and behaviour on cigarette and HTP among youth. METHODS: The study was conducted in February and March 2019 inside Sapienza University of Rome and high school Giulio Cesare of Rome. A self-administered anonymous questionnaire was performed to investigate smoking habits and measures knowledge about HTP among Italian teenagers. OUTCOMES: A sample of 60 students took part in the validation of the questionnaire. The overall Cronbach's alpha was 0,635, corresponding to a sufficient reliability. CONCLUSIONS: There is little or no data on consumption or perceptions of HTP products among youth and evidence suggests the usefulness of a standardized and validated questionnaire available to monitoring of awareness, interest in trying and prevalence of use of these novel products among young people.

[Changes in infant sleeping position after an educational intervention in a University General Hospital during a ten year follow up]. / Cambios en la posición al dormir para la prevención de la muerte súbita del lactante: diez años de seguimiento.

INTRODUCTION: The prone sleeping position has been identified as the main risk factor for the sudden infant death syndrome (SIDS). OBJECTIVES: The aim was to assess the prevalence of the different sleeping positions of infants, between 1 and 6 months, who attended the immunizations office of the "Hospital Italiano de Buenos Aires" during a ten year period. During this time an important educational intervention, called "Project Link" was developed. MATERIAL AND METHODS: An analytical, prospective study was developed. The recommended position (RP) was the supine position,as well as the side position, to place infants to sleep. Mothers were advised to avoid the prone position or a non-recommended position (NRP). RESULTS: A hundred completed questionnaires were obtained each year in 1996, 1998-2001, 2004 and 2006. The percentage of mothers who placed their infants in sleep supine was 49 % in 1996 vs. 90 % in 2006 (p = 0.0001). The accomplishment of the RP was divided in two periods: 1996-1998 (59 %) and 1999-2006 (88 %), p = 0.0002. CONCLUSIONS: The prevalence of the infant prone sleeping position reduced gradually in the studied population. Nevertheless, it is imperative to emphasize the benefits of the RP, because only during 1999 and 2004 was the percentage of prone position less than 10 %, as in developed countries.

Computed tomographic features of urinary bladder torsion in two dogs.

Urinary bladder torsion is rare in dogs. It is characterised by rotation of the organ along its longitudinal axis and is potentially life-threatening because of urinary flow obstruction with subsequent urine retention, hydroureter, hydronephrosis and azotaemia. This report describes the computed tomographic features of urinary bladder torsion in two dogs. In both cases, the hallmark indicative of torsion was the "whirl sign," originating from the twisted pelvic urethra and urinary bladder neck encircling the ureters, blood vessels and bladder ligaments in a characteristic spiral pattern. The imaging features correlated well with surgical findings, demonstrating high sensitivity of computed tomography in the preoperative diagnosis of urinary bladder torsion.

The activity of differentiation factors induces apoptosis in polyomavirus large T-expressing myoblasts.

It is commonly accepted that pathways that regulate proliferation/differentiation processes, if altered in their normal interplay, can lead to the induction of programmed cell death. In a previous work we reported that Polyoma virus Large Tumor antigen (PyLT) interferes with in vitro terminal differentiation of skeletal myoblasts by binding and inactivating the retinoblastoma antioncogene product. This inhibition occurs after the activation of some early steps of the myogenic program. In the present work we report that myoblasts expressing wild-type PyLT, when subjected to differentiation stimuli, undergo cell death and that this cell death can be defined as apoptosis. Apoptosis in PyLT-expressing myoblasts starts after growth factors removal, is promoted by cell confluence, and is temporally correlated with the expression of early markers of myogenic differentiation. The block of the initial events of myogenesis by transforming growth factor beta or basic fibroblast growth factor prevents PyLT-induced apoptosis, while the acceleration of this process by the overexpression of the muscle-regulatory factor MyoD further increases cell death in this system. MyoD can induce PyLT-expressing myoblasts to accumulate RB, p21, and muscle- specific genes but is unable to induce G0(0) arrest. Several markers of different phases of the cell cycle, such as cyclin A, cdk-2, and cdc-2, fail to be down-regulated, indicating the occurrence of cell cycle progression. It has been frequently suggested that apoptosis can result from an unbalanced cell cycle progression in the presence of a contrasting signal, such as growth factor deprivation. Our data involve differentiation pathways, as a further contrasting signal, in the generation of this conflict during myoblast cell apoptosis.

Neurological manifestations in dogs naturally infected by Leishmania infantum: descriptions of 10 cases and a review of the literature.

In order to evaluate possible nervous system involvement in canine leishmaniasis, retrospective evaluation of all medical records of leishmaniotic dogs exhibiting neurological signs referred to our hospital over a 5-year period was performed. The records of 10 dogs were reviewed. Depending on the neuroanatomical localisation, the dogs underwent advanced diagnostic imaging, cerebrospinal fluid analysis, electrodiagnostic testing and histopathologic evaluations. The final neurological diagnosis was: meningoencephalitis (n=2), brain haemorrhagic stroke (n=1), haemorrhagic choroiditis (n=1), meningomyelitis (n=2), ischaemic myelopathy (n=1), polymyositis (n=2) and peripheral neuropathy (n=1). This study confirms that both central and peripheral nervous systems can be affected by leishmaniasis and provides an overview on the possible etiopathogenetic mechanisms. In addition, clinical and diagnostic findings, therapy and follow-up of affected dogs are described.

Work- related Stress, over-nutrition and cognitive disability.

Work-related stress may exert a negative impact on a variety of physical and psychological attributes relating to the health of employees and work organizations. Several studies conducted in Italy have shown that workers and employees who express less satisfaction show increased symptoms of obesity and cognitive disability. The latest evidence underlines the pathogenic relationship between stress and neurological disease through inflammatory neuro- immune activation. The aim of this review was to describe the relationship between workplace stress and adverse changes in lifestyle that develop into obesity, neuroinflammation and cognitive dysfunction. The molecular mechanisms involved and guidelines for the prevention of these trends are discussed briefly.

Psychopathology and neoplastic disease: medico-social and medico-legal considerations.

The cognitive disability associated with stress in patients presenting cancer disease may exert a significant impact on the psychological health of the individual and even deteriorate the clinical diagnosis. The present study consists of a review of the available literature and an analysis of the association between psychopathologic disease and cancer by selecting useful contributions to the medicosocial discussion of the topic. Interesting considerations have emerged on the epidemiology and pathogenesis of the association between psychopathology and cancer that initiated possibilities towards a greater accuracy in the assessment of the patient that is not only limited to oncologic problems and outcomes.

Preclinical Antileukemia Activity of Tramesan: A Newly Identified Bioactive Fungal Metabolite.

Despite improvements that occurred in the last decades in the acute myeloid leukemia (AML) treatment, clinical results are still unsatisfactory. More effective therapies are required, and innovative approaches are ongoing, including the discovery of novel antileukemia natural compounds. Several studies have described the activity of extracts from mushrooms which produce compounds that exhibited immunological and antitumor activities. The latter has been demonstrated to be promoted in vitro by mushroom polysaccharides via induction of apoptosis. However, the antileukemia activity of these compounds on primary cells is still not reported. In the present study, we examined the in vitro effects of Tramesan (TR), a bioactive compound extracted from Trametes versicolor, on leukemic cell lines and primary cells. Our results demonstrated that TR induced a marked growth inhibition of leukemic cell lines and primary cells from AML patients. The antiproliferative effects of TR were associated in primary AML cells with a significant increase of apoptosis. No significant cytotoxic effects were observed in normal peripheral blood mononuclear cells (MNC) from healthy donors. Our data demonstrated a cytotoxic activity of TR on leukemia cells prompting further translational applications. Ongoing studies are elucidating the molecular mechanisms underlying its antileukemic activity.

Quantitative single cell determination of ERK phosphorylation and regulation in relapsed and refractory primary acute myeloid leukemia.

We investigated the constitutive activation of the MEK/ERK pathway in acute myelogenous leukemia (AML) via a flow cytometric technique to quantitate expression of phosphorylated ERK (p-ERK). A total of 42 AML samples (16 newly diagnosed, 26 relapsed/refractory) were analyzed. Normal bone marrow CD34+ cells (n = 10) had little or no expression of p-ERK, while G-CSF-mobilized CD34+ cells exhibited enhanced p-ERK levels. Markedly elevated p-ERK levels were found in 83.3% of the AML samples, with no differences observed between the newly diagnosed and relapsed/refractory samples. Treatment with a MEK inhibitor resulted in significantly decreased p-ERK levels in both the newly diagnosed and relapsed/refractory samples, which was associated with growth arrest, but not apoptosis induction. In summary, we defined conditions for the analysis of MAPK signaling in primary AML samples. Normal CD34+ cells expressed very low levels of p-ERK, and increased p-ERK levels were found in normal G-CSF-stimulated circulating CD34+ cells. Constitutively high p-ERK levels observed in the majority of AML samples suggest deregulation of this pathway that appears to be independent of disease status. The ability of ERK inhibition to promote growth arrest rather than apoptosis suggests that clinical trials of MEK/ERK inhibitors may be more effective when combined with chemotherapy.

Splenophrenic portosystemic shunt in dogs with and without portal hypertension: can acquired and congenital porto-caval connections coexist?

The possible existence of the same pattern of porto-caval connection in dogs having a single congenital portosystemic shunt (CPSS) and in dogs having multiple acquired portosystemic shunt (MAPSS) secondary to portal hypertension (PH) was evaluated. Retrospective evaluation of all CT examinations of patients having portosystemic shunt (PSS) was performed in a 4-year time period. All anomalous porto-caval connections were assessed for anatomical pattern and compared with published veterinary literature. Records of 25 dogs were reviewed. 16 dogs had a single CPSS (CPSS group), and 9 dogs had multiple acquired PSS secondary to PH (APSS group). The splenophrenic shunt pattern was found in 3 dogs of the CPSS group as a single congenital anomaly without PH and in 2 dogs of the APSS group associated with MAPSS and ascites due to different hepatic diseases causing PH. These findings corroborate two hypotheses: 1) Splenophrenic PSS should be considered as a classical CPSS but if this is not sufficient to alleviate a PH developed after birth because of eventual hepatic or portal diseases, in this case ascites and acquired portal collaterals may develop. In this case, MAPSS and CPSS may coexist. 2) The pattern of splenophrenic PSS, classically described among CPSS, may develop as acquired portal collateral in dogs with PH and it should also be included in the category of APSS. These preliminary findings may be helpful in reconsidering the classical haemodynamics of porto-caval diseases, enrich the classification of APSS in dogs and refine the imaging evaluation of patients with PH.

Osteopontin expression in healing wounds of horses and in human keloids.

REASONS FOR PERFORMING STUDY: Convincing evidence shows that persistent or excessive expression of osteopontin (OPN) is linked to fibroproliferation of various organs in laboratory animals and in man, such that its downregulation is a logical therapeutic objective. OBJECTIVES: To investigate OPN expression in an equine model of wound healing and in clinical specimens of equine exuberant granulation tissue and human keloids in an effort to better understand the contribution of this protein to inflammation-associated skin fibrosis. STUDY DESIGN: Description of gene and protein expression in an experimental equine model of wound healing and clinical specimens in horse and man. METHODS: Osteopontin gene expression was evaluated by quantitative PCR, while protein expression was investigated by means of immunohistochemical staining. RESULTS: Quantitative PCR showed that the OPN gene is expressed in normal intact skin of horses and continues to be expressed during the wound-healing process. An increase in gene expression was observed throughout the phases of wound healing, with a final decrease at wound closure. The protein was not detected in normal skin. Keratinocytes in wound-edge samples did not express the protein, whereas dermal immunoreactivity was confined to inflammatory cells. Healed wounds were devoid of staining. Equine exuberant granulation tissue showed immunoreactivity of the surrounding epidermis, infiltrating neutrophils, mononuclear cells, endothelial cells and fibroblasts. Human keloids showed OPN immunoreactivity throughout the epidermis as well as in mononuclear cells and scattered fibroblasts. CONCLUSIONS: Immunohistochemical data show a different pattern of expression between normally healing and fibrotic wounds (exuberant granulation tissue and keloids), thus suggesting a role in fibroproliferation in horses and man.