ADRIS: The new open-source accessible driving simulator for training and evaluation of driving abilities.

BACKGROUND AND OBJECTIVE: Independent living and transportation are crucial aspects for people living with a disability. After an injury, it is important to assess driving ability, in terms of physical and psychological conditions, and to test the effects of prescribed drugs. Within this framework, driving simulators are suitable tools for training driving skills; however, available tools are expensive or lack appropriate sets of behavioral measures to fully characterize the drivers' ability. METHODS: This work presents the first step toward the development of ADRIS, a new open-source, accessible, realistic virtual reality simulator for training and testing driving skills of people with sensory-motor disability. This includes a prototype based on an open-source simulator for autonomous driving research (CARLA), with the addition of customized features such as adaptable driving controllers, a virtual reality headset, and the possibility to collect behavioral and physiological data. Also, the new system allows to set different environmental conditions, to include and control the timing of potentially dangerous situations, and to set scenarios with various difficulty levels. RESULTS: Tests on 17 healthy participants demonstrated that the simulator is well tolerated in terms of discomfort, physical fatigue, and mental effort. Also, the system is easy to use and is capable of providing a realistic driving experience, allowing the extraction of reliable behavioral parameters. CONCLUSIONS: ADRIS combines a high-fidelity virtual world, with customizable features specifically designed for the training and testing of people living with a disability, thus making it usable in many contexts such as home training, rehabilitation, education, and research.

Expression of the epidermal stem cell marker p63/CK5 in cutaneous papillomas and cutaneous squamous cell carcinomas of dogs.

Cutaneous papillomas (CPs) and cutaneous squamous cell carcinomas (CSCCs) are usual epidermal tumours in dogs. CPs and CSCCs probably arise from the neoplastic transformation of the keratinocytes within the stem cell compartment, since these cells are the only keratinocytes that would reside long enough to accumulate the number of molecular alterations to drive the progression towards a tumour cell phenotype. However, the role of these cells in common epidermal tumours in dogs is still unknown. Thus, the purpose of this study was to evaluate the immunohistochemical expression pattern of p63 together with CK5, molecular markers of epidermal stem cells, on sections of tissue microarrays constructed from canine samples of CP and CSCC to investigate the contribution of stem cells in those canine tumours. p63/CK5 coexpression was retained in most basal and some suprabasal cells in CPs and CSCCs. In addition, increased coexpression of these molecules was observed in a group of CPs and CSCCs, as a result of a higher p63 expression. These results suggest that the coexpression of p63/CK5 may mark epidermal keratinocytes that possess self-renewal capacity rather than only stem cells, and suggest that transit amplifying cells, and even differentiated keratinocytes, may also contribute to the pathogenesis of epidermal tumours in dogs.

An SEM compatible plasma cell for in situ studies of hydrogen-material interaction.

An in situ hydrogen (H) plasma charging and in situ observation method was developed to continuously charge materials, while tensile testing them inside a scanning electron microscope (SEM). The present work will introduce and validate the setup and showcase an application allowing high-resolution observation of H-material interactions in a Ni-based alloy, Alloy 718. The effect of charging time and pre-straining was investigated. Fracture surface observation showed the expected ductile microvoid coalescence behavior in the uncharged samples, while the charged ones displayed brittle intergranular and quasi-cleavage failure. With the in situ images, it was possible to monitor the sample deformation and correlate the different crack propagation rates with the load-elongation curves. H-charging reduced the material ductility, while increasing pre-strain decreased hydrogen embrittlement susceptibility due to the possible suppression of mechanical twinning during the tensile test and, therefore, a reduction in H concentration at grain and twin boundaries. All the presented results demonstrated the validity of the method and the possibility of in situ continuously charging of materials with H without presenting any technical risk for the SEM.

Aberrant Expression of E-cadherin/ß-catenin During Epidermal Tumourigenesis in Dogs.

Clinically relevant epidermal tumours in dogs include cutaneous papillomas (CPs) and cutaneous squamous cell carcinomas (CSCCs). The development of CPs and CSCCs involves dysregulation in expression of E-cadherin/ß-catenin; however, knowledge about the contribution of these molecules to epidermal tumourigenesis in dogs is limited. This study examined the immunohistochemical expression pattern of E-cadherin/ß-catenin in samples of normal canine epidermis, CPs, preneoplastic epidermis and CSCCs, using tissue microarrays, in order to elucidate whether the dysregulated expression of these molecules may contribute to the pathogenesis of clinically relevant epidermal tumours in dogs. We also investigated the correlation between the immunohistochemical expression pattern of E-cadherin/ß-catenin in these tissue microarrays to further evaluate whether the disruption of the adherens junction interactions plays a relevant role in canine epidermal tumourigenesis. In samples of CP and preneoplastic epidermis, the membrane immunoreactivity of E-cadherin/ß-catenin was conserved, while in CSCC, the immunoreactivity of these molecules was significantly reduced, independently of the tumour location. There was significant correlation between the membrane expression of E-cadherin/ß-catenin in CSCC. ß-catenin also showed cytoplasmic and nuclear expression in samples of CP, preneoplastic epidermis and CSCC. These results support the hypothesis that dysregulated expression of E-cadherin/ß-catenin may play a critical role in the pathogenesis of relevant canine epidermal tumours, not only due to the disruption of the intercellular adherens junctions, but also due to the dysregulated activity of the signalling pathways in which these molecules are involved.

Dysregulated Expression of Phosphorylated Epidermal Growth Factor Receptor and Phosphatase and Tensin Homologue in Canine Cutaneous Papillomas and Squamous Cell Carcinomas.

The molecular mechanisms contributing to the development of cutaneous papillomas (CPs) and cutaneous squamous cell carcinomas (CSCCs) are still poorly understood, limiting the ability to identify molecular suitable targets for the development of novel therapies. Persistent activation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway is a component of epidermal carcinogenesis in dogs. The present study describes the immunohistochemical expression pattern of two key regulatory molecules involved in the PI3K/Akt/mTOR signalling pathway, phosphorylated epidermal growth factor receptor (pEGFR)Tyr1068 and phosphatase and tensin homologue (PTEN), in samples of normal canine epidermis, CP, preneoplastic epidermis and CSCC using tissue microarrays to determine whether the deregulated activity of these molecules is involved in the pathogenesis of these relevant epidermal tumours of dogs. Expression of pEGFR and PTEN was dysregulated in most samples of CP, preneoplastic epidermis and CSCC. Overexpression of pEGFR, together with decreased expression of PTEN, may facilitate the progression of some canine CPs and CSCCs by deregulation of the key cellular functions in which the PI3K/Akt/mTOR signalling pathway is involved. These findings suggest that the PI3K/Akt/mTOR signalling molecules may be potential therapeutic targets for canine patients with CP and CSCC.

Immunohistochemical expression of selected phosphoproteins of the mTOR signalling pathway in canine cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) represents one of the most common malignant skin tumors in dogs. Research aimed at clarifying how the deregulated activity of signalling pathways contributes to cSCC progression can help to identify molecular suitable targets for the development of novel therapies. The present study describes the immunohistochemical expression pattern of two proteins (pAktSer473 and pS6Ser235/236, the latter combined with Ki-67) involved in the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway in canine specimens of normal epidermis, pre-neoplastic epidermis, and cSCC using tissue microarrays. The results suggest that the PI3K/Akt/mTOR signalling pathway has a low expression in the normal canine epidermis, and that selected molecules involved in this signalling pathway are dysregulated during the canine epidermal carcinogenesis process. These findings provide important evidence that the persistent activation of the PI3K/Akt/mTOR signalling pathway represents one of the key events during cSCC progression in canine patients, pointing to the PI3K/Akt/mTOR pathway as a potential therapeutic target.

Reliability of the Italian version of the International Spinal Cord Injury Pain Basic Data Set.

STUDY DESIGN: Multicentric prospective psychometric study. OBJECTIVE: To provide a translation of the International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS) for Italian persons and to evaluate the interrater reliability of the translated version. SETTING: Ten Italian rehabilitation centres specialized in spinal injury care. METHODS: The initial translation was performed by two medical doctors who had an in-depth knowledge of spinal cord injury (SCI), and then a back translation (from Italian to English) was given to an accredited agency. Sixty-six participants with SCI (53 men, 13 women; mean ± SD age: 53.4 ± 16.0 years) were evaluated by means of the Italian version of the ISCIPBDS by two different examiners. Intraclass correlation coefficient (ICC) or Cohen's Kappa (ĸ) was calculated to test the interrater agreement for the test-retest cases. RESULTS: All 66 participants had at least one pain problem and 34% of them had only one type of pain. A good interrater agreement was obtained in terms of number of pain (ICC = 0.781), type of pain (ĸ = 0.683), pain intensity (ICC = 0.798), correspondence of pain localization (ĸ = 0.750), and the value of the pain interference in day-to-day activities, overall mood and night's sleep (ICC = 0.827, ICC = 0.861 and ICC = 0.724, respectively). Eventually a prominent prevalence of neuropathic pain was recorded (64% from the first examiner and 62% from the second one). CONCLUSIONS: The authors propose the Italian version of ISCIPBDS that can be used for research and clinical evaluation of pain in SCI persons; it shows a significant interrater reliability.

Changes in neuromuscular activity during motor training with a body-machine interface after spinal cord injury.

Body machine interfaces (BMIs) are used by people with severe motor disabilities to control external devices, but they also offer the opportunity to focus on rehabilitative goals. In this study we introduced in a clinical setting a BMI that was integrated by the therapists in the rehabilitative treatments of 2 spinal cord injured (SCI) subjects for 5 weeks. The BMI mapped the user's residual upper body mobility onto the two coordinates of a cursor on a screen. By controlling the cursor, the user engaged in playing computer games. The BMI allowed the mapping between body and cursor spaces to be modified, gradually challenging the user to exercise more impaired movements. With this approach, we were able to change our subjects' behavior, who initially used almost exclusively their proximal upper body-shoulders and arms - for using the BMI. By the end of training, cursor control was shifted toward more distal body regions - forearms instead of upper arms - with an increase of mobility and strength of all the degrees of freedom involved in the control. The clinical tests and the electromyographic signals from the main muscles of the upper body confirmed the positive effect of the training. Encouraging the subjects to explore different and sometimes unusual movement combinations was beneficial for recovering distal arm functions and for increasing their overall mobility.

First report of cerebellar abiotrophy in an Arabian foal from Argentina.

Evidence of cerebellar abiotrophy (CA) was found in a six-month-old Arabian filly with signs of incoordination, head tremor, wobbling, loss of balance and falling over, consistent with a cerebellar lesion. Normal hematology profile blood test and cerebrospinal fluid analysis excluded infectious encephalitis, and serological testing for Sarcocystis neurona was negative. The filly was euthanized. Postmortem X-ray radiography of the cervical cephalic region identified not abnormalities, discounting spinal trauma. The histopathological analysis of serial transverse cerebellar sections by electron microscopy revealed morphological characteristics of apoptotic cells with pyknotic nuclei and degenerate mitochondria, cytoplasmic condensation and areas with absence of Purkinje cells, matching with CA histopathological characteristics. The indirect DNA test for CA was positive in the filly, and DNA test confirmed the CA carrier state in the parents and the recessive inheritance of the disease. To our knowledge this is the first report of a CA case in Argentina.

An automatic method for atom identification in scanning tunnelling microscopy images of Fe-chalcogenide superconductors.

We describe a computational approach for the automatic recognition and classification of atomic species in scanning tunnelling microscopy images. The approach is based on a pipeline of image processing methods in which the classification step is performed by means of a Fuzzy Clustering algorithm. As a representative example, we use the computational tool to characterize the nanoscale phase separation in thin films of the Fe-chalcogenide superconductor FeSex Te1-x , starting from synthetic data sets and experimental topographies. We quantify the stoichiometry fluctuations on length scales from tens to a few nanometres.

Enhanced visual acuity with echogenic needles in ultrasound-guided axillary brachial plexus block: a randomized, comparative, observer-blinded study.

BACKGROUND: We prospectively evaluated the effect of insertion angle on the visibility of echogenic and nonechogenic needles in phantoms and in axillary nerve blocks in patients. METHODS: Conventional and echogenic needles were studied in phantoms at insertion angles of 0-30°, 30-45°, and ≥ 45°. Operators rated comfort and image quality during the procedure and experts blinded to the needle groups randomly analyzed videos for tip and shaft visibility, surrounding tissue visibility, sharpness of the needle surface, and percentage of time with the needle completely visible. Patients scheduled for axillary nerve block were prospectively enrolled in the clinical study. Needle insertion angles were 0-30° for the median nerve approach, 30-45° for the radial nerve, and ≥ 45° for the musculocutaneous nerve. The same needle parameters were analyzed during the procedure and on videos. RESULTS: Physician comfort and image quality were significantly better for echogenic needles for phantoms and patients at 30-45° and ≥ 45° insertion angles. Needle tip and shaft visibility at 30-45° and ≥ 45° insertion angles in phantoms and for the musculocutaneous nerve in patients were significantly improved, as well as the percentage with complete needle visualization during the procedure. Tissue visibility and needle sharpness were significantly superior for conventional needles. There were no differences concerning block parameters and adverse events. CONCLUSION: Needles with enhanced echogenicity improved physician comfort, image quality, needle visibility, and visualization time of the needle during ultrasound-guided procedures in phantoms and axillary nerve blocks using insertion angles of 30-45° and ≥ 45°.

Paraplegia in a patient with Von Hippel Lindau syndrome: surgical and reconstructive treatment of Marjolin's ulcer. A case report.

STUDY DESIGN: Marjolin's ulcer is a squamous cell carcinoma that develops in posttraumatic scars and chronic wounds. Suspicion of such lesions should be raised in chronic wounds demonstrating characteristic changes. We have reported the peculiar phenomenon of malignant transformation of chronic pressure sores that occurred in a paraplegic patient. OBJECTIVES: The aim of this study was to cover the extensive defects by a last resort reconstructive option. SETTING: Department of Plastic and Reconstructive Surgery, Università Politecnica delle Marche, Ancona, Italy. METHODS AND RESULTS: A 40-year-old paraplegic man, with multiple hemangioblastomas of the brain and spinal cord due to Von Hippel Lindau syndrome developed pressure ulcers with unstable healing over the sacral, trochanteric, bilateral, and ischiatic areas after 15 years from neurosurgery. The biopsy result showed an invasive squamous carcinoma. Carcinomas in pressure sores are highly aggressive, and they need to be treated more radically. In our case we opted for a demolitive surgical treatment including musculocutaneous rotational flap harvested from total left thigh to cover the extensive defects. The limb was previously disarticulated. CONCLUSION: In Marjolin's ulcer, multiple biopsies are the first-line modality for the early diagnosis as they are a safe method with high rate of accuracy. First-line treatment is surgery consisting of radical excision with lymph node dissection, if they are involved. Adjuvant radiation therapy may be used in selected patients. Management of massive pelvic defects can be a challenging problem. The pedicled lower limb flap offers a technique that can be considered as a last resort procedure for extensive defects where other options are insufficient or not available anymore. In our case the patient is disease-free after 2 years of follow-up.

Lack of prognostic significance of angiogenesis in canine melanocytic tumours.

The prognostic significance of angiogenesis in some canine tumours has been investigated, but little is known about its relevance in canine melanocytic tumours (MTs). The aim of this study was to evaluate the prognostic significance of angiogenesis in canine MTs. A total of 36 cutaneous melanocytomas (benign MTs), 40 cutaneous melanomas (malignant MTs) and 43 oral melanomas were studied. Survival data were available for a subset of 59 cases. Microvessel density (MVD) and endothelial area (EA) were determined by immunolabelling using an antibody specific for von Willebrand factor (vWF). Mean MVD (expressed as the number of microvessels per mm(2)) was 129 ± 14 in melanocytomas, 191 ± 16 in cutaneous melanomas and 208 ± 16 in oral melanomas. Mean EA (expressed as the percentage of the total area) was 1.5 ± 0.14 in melanocytomas, 2.6 ± 0.2 in cutaneous melanomas and 2.4 ± 0.3 in oral melanomas. The differences in MVD and EA between melanocytomas and melanomas were significant (P = 0.001 and P = 0.003, respectively). MVD and EA were significantly correlated between cutaneous and oral MTs (r = 0.54; P <0.001 and r = 0.63; P <0.001, respectively). MVD and EA were not related to survival in cutaneous and oral MTs. In conclusion, tumour vascularization was higher in melanomas than in melanocytomas, but it seemed to have no prognostic significance in these tumours.

A simple method of infecting rabbits with Bovine herpesvirus 1 and 5.

This report describes an alternative technique to inoculate rabbits and to reproduce infection by Bovine herpesvirus 1 and 5. First, the nostrils are anaesthetized by aspersion with local anaesthetic. A few seconds later, and after proving the insensitivity of the zone, the rabbits are put on their back legs with their nostrils upwards and the inoculum is introduced slowly into each nostril by using disposable droppers. Clinical signs, viral isolation from nasal swabs, histological lesions found, positive polymerase chain reaction and antibodies production confirm the infection. This very simple and bloodless technique, where the animals are exposed to minor distress, may be useful for evaluating the virulence of BoHV-1 and BoHV-5 strains, to study the establishment of latent virus infection and to test the potential of experimental vaccines or properties of antiviral drugs. It may be also suitable for experimental infection with other respiratory viruses in this animal model.

Hyperhidrosis treatment with bornaprine in the acute phase of spinal cord-injured patients.

STUDY DESIGN: Original article. OBJECTIVE: To test the use of bornaprine in the hyperhidrosis treatment in the acute phase of spinal cord-injured patients. SETTING: Patients with acute spinal cord lesions in the Spinal Unit of Pietra Ligure, Savona, Italy. METHOD: In 4 years, 12 patients have been treated, for a maximum period of 75 days, with dosages ranging from 2 to 4 mg day(-1). RESULTS: All of them reported long-lasting subjective benefits, without side effects, even after the interruption of the therapy. CONCLUSION: The bornaprine treatment, at 2 or 4 mg day(-1) dosage, has been effective and safe to contrast hyperhidrosis, in the acute phase of spinal cord-injured patients. This positive experience would require additional trials and a larger number of cases to gain a more solid support.

Primary pulmonary adenocarcinoma metastatic to the uvea, brain and adrenal gland in a dog.

A 10-year-old male Briard dog was presented because of listlessness, abnormal gait, fever, inappetence, and seizures. A non-pigmented growth was observed in the ventral quadrant of the left iris. Thoracic radiographs revealed multiple pulmonary metastases and the owner opted for killing. On necropsy, lung masses and nodules in left iris, right adrenal medulla, and brain were detected. Histologically the primary tumour was diagnosed as pulmonary adenocarcinoma with predominant solid pattern. Metastases to regional lymph nodes, uvea, adrenal medulla, and brain were recognized. The metastatic behaviour resembled that occurring in humans. To the authors' knowledge, this is the first report of a pulmonary adenocarcinoma with metastasis to the uvea in a dog.

Cutaneous lymphangiosarcoma in a young dog: clinical, anatomopathological and lectinhistochemical description.

Lymphangiosarcoma is a rare tumour in domestic animals arising from lymphatic endothelial cells. Occasionally, microscopic differentiation with haemangiosarcoma may be difficult. The aim of the present study was to describe a lymphangiosarcoma in a 1-year-old female Doberman Pinscher dog and to characterize its lectinhistochemical binding pattern as compared with that of haemangiosarcoma. The dog was presented because of a cutaneous painful swelling located in the left axilla. Histological diagnosis confirmed lymphangiosarcoma. The dog was killed. Necropsy revealed mediastinal lymph nodes' involvement. Twenty lectins were tested in tissue sections of this case as well as in four haemangiosarcomas from other dogs. Staining intensity was issued upon optical density determinations. Percentage of lectinhistochemical staining area was also conducted. RCA-I showed the most intense and wide distributed labelling pattern for lymphangiosarcoma. PHA-E was the counterpart for haemangiosarcoma. Should similar results be obtained in further studies, such differences could aid in the differential diagnosis between lymphangiosarcoma and haemangiosarcoma when histological pictures were not conclusive.

Peripheral neuroblastoma in a newborn piglet.

Peripheral neuroblastoma (PNB) is a rare neoplasia derived from neuroepithelial cells. PNB typically presents as a greyish mass, composed of round cells with features of neuronal differentiation. Necropsy, performed on a 1-day-old piglet, revealed a mass craniodorsally located in the abdominal cavity. Histologically, the predominant population consisted of small round to ovoid cells with scanty cytoplasm and dark round nuclei, besides, there were larger neurone-like cells. Neurone-specific enolase and S-100 protein were immunohistochemically detected, while glial fibrillary acidic protein was negative. Histological and immunohistochemical findings substantiated the diagnosis of a grade II peripheral neuroblastoma. This seems to be the first description of a PNB in a newborn piglet.

Paratuberculosis in red deer (Cervus elaphus): an immunohistochemical study.

In the present study, we compared the utility of immunohistochemistry with serological and histological results for the characterization of Mycobacterium avium ssp. paratuberculosis (M. paratuberculosis) in tissues of affected red deer. Bacterial isolation was considered the standard reference. Samples were taken from seven clinically affected animals with typical macroscopic lesions. The enzyme linked immunosorbent assay (ELISA) and the gel diffusion tests (GD) were used for serological determinations. Samples from intestine and mesenteric lymph nodes were processed for bacterial isolation and histology. M. paratuberculosis was isolated from all the animals. Histologically, lymph nodes displayed necrosis and mineralization at the cortical and medullar areas. Ziehl-Neelsen stained bacteria were numerous inside macrophages and Langhans-type giant cells. Giant and epithelioid cells and lymphocytes were prominent at the ileal mucous membrane. The immunostaining of M. paratuberculosis was very clear inside epithelioid and giant cells. Image analysis was carried out to determine the immunostained area. There was total agreement among the methods employed. Immunohistochemistry can be very useful when the microorganism cannot be recovered from tissues or faeces.

Effects of plant-induced hypervitaminosis D on cutaneous structure, cell differentiation and cell proliferation in cattle.

Solanum glaucophyllum (Sg) (synonym S. malacoxylon) is a plant toxic to cattle due to its high levels of 1,25-dihydroxyvitamin D3 as glycoside derivatives. Sg causes a disease characterized by wasting and calcification of soft tissues. The effects of vitamin D are not only important in calcium homeostasis, but also in immune regulation, cell growth and cell differentiation. Skin samples in Sg-intoxicated and control heifers were studied histologically. Cellular differentiation and proliferation were analysed by immunohistochemical expression of cytokeratins, involucrin and proliferating cell nuclear antigen (PCNA). The results were obtained by image processing and analysis and were statistically evaluated. Sg-intoxicated cattle showed atrophy of epidermis and severe involution of hair follicles and of sebaceous and sweat glands. As judged by PCNA expression, cellular proliferation was reduced, even though the reduction was not statistically significant. The analysed markers of differentiation, e.g. involucrin and cytokeratins 10 and 11, changed in relation to Sg-poisoning. The possible pathogenesis of the skin lesions is discussed.