Respiratory failure and pharyngeal hematoma as presenting signs of Moschcowitz's syndrome: a case report and literature review.

Moschcowitz's syndrome or thrombotic thrombocytopenic purpura is a quite rare pathology in childhood, being, as a matter of fact, more frequent among adult people. Often it is hard to distinguish from other pathologies in children both for its rare incidence and for the presence of clinical forms that are very heterogeneous and difficult to be classified. We report on a 13 year-old girl suffering from Moschcowitz's syndrome, in whom respiratory failure and pharyngeal hematoma were the first sign of the disease follone by jaundice, hematoma of the arm and limbs. The girl was treated with plasmapheresis with an improvement of her general condition. Since then we have followed up the girl for two years without any reappearance of the symptomatology. To our knowledge this is the first report of this peculiar presentation in children.

Rehabilitation of focal hand dystonia in musicians: a systematic review of the studies. / Rehabilitación de la distonía focal de mano en músicos: una revisión sistemática de los estudios.

INTRODUCTION: Focal hand dystonia in musicians is a task-specific movement disorder characterized by an involuntary loss of control and coordination of finger movements during instrumental playing. MATERIALS AND METHODS: Literature searches with the keywords 'dystonia' AND 'musician' AND 'finger' OR 'treatment' OR 'therapy' OR 'rehabilitation' were conducted in PubMed, EMBASE, Cochrane Library and Web of Science to perform the systematic review about the several strategies used to treat dystonia in musicians. The search was performed independently by two authors (R.C. and M.V.) from 6 April 2020 till 6 June 2020. The research identified a total of 423 articles. Seventy-seven selected articles were analysed by the reviewers. Thirty-six publications met the inclusion criteria and were included in the systematic review. RESULTS: The systematic review was performed to identify the main used treatments for dystonia in musicians. We defined the several techniques to better guide the physician to delineate a rehabilitation protocol adopting the better strategies described in the current literature. CONCLUSION: This systematic review tried to provide to the reader a complete overview of the literature of all possible different treatments for dystonia in musicians. A correct protocol could permit to improve the motor performance and the quality of life of musicians.

TITLE: Rehabilitación de la distonía focal de mano en músicos: una revisión sistemática de los estudios.Introducción. La distonía focal de la mano en los músicos es un trastorno del movimiento relacionado con una tarea específica, que se caracteriza por una pérdida involuntaria del control y la coordinación de los movimientos de los dedos al tocar un instrumento. Materiales y métodos. Se llevaron a cabo búsquedas bibliográficas con las palabras clave 'dystonia' (distonía) Y 'musician' (músico) Y 'finger' (dedo) O 'treatment' (tratamiento) O 'therapy' (terapia) O 'rehabilitation' (rehabilitación) en PubMed, EMBASE, Cochrane Library y Web of Science para realizar la revisión sistemática sobre las diversas estrategias usadas para tratar la distonía en los músicos. La búsqueda se realizó de forma independiente por dos autores (R.C. y M.V.) entre el 6 de abril de 2020 y el 6 de junio del mismo año. La investigación identificó un total de 423 artículos. Los encargados de la revisión analizaron 77 artículos que fueron previamente seleccionados. Treinta y seis publicaciones cumplieron con los criterios de inclusión y se incluyeron en la revisión sistemática. Resultados. La revisión sistemática se realizó para identificar los principales tratamientos utilizados para la distonía en músicos. Se definieron las diversas técnicas existentes para orientar mejor a los médicos a la hora de diseñar un protocolo de rehabilitación que adopte las mejores estrategias descritas en la bibliografía actual. Conclusión. Esta revisión sistemática intenta proporcionar al lector una mirada completa sobre todos los posibles tratamientos diferentes para la distonía en los músicos. Un protocolo correcto podría permitir mejorar el rendimiento motor y la calidad de vida de los músicos.

Oxidative stress, redox homeostasis and cellular stress response in Ménière's disease: role of vitagenes.

Ménière's disease (MD) is characterized by the triad of fluctuating hearing loss, episodic vertigo and tinnitus, and by endolymphatic hydrops found on post-mortem examination. Increasing evidence suggests that oxidative stress is involved in the development of endolymphatic hydrops and that cellular damage and apoptotic cell death might contribute to the sensorineural hearing loss found in later stages of MD. While excess reactive oxygen species (ROS) are toxic, regulated ROS, however, play an important role in cellular signaling. The ability of a cell to counteract stressful conditions, known as cellular stress response, requires the activation of pro-survival pathways and the production of molecules with anti-oxidant, anti-apoptotic or pro-apoptotic activities. Among the cellular pathways conferring protection against oxidative stress, a key role is played by vitagenes, which include heat shock proteins (Hsps) as well as the thioredoxin/thioredoxin reductase system. In this study we tested the hypothesis that in MD patients measurable increases in markers of cellular stress response and oxidative stress in peripheral blood are present. This study also explores the hypothesis that changes in the redox status of glutathione, the major endogenous antioxidant, associated with abnormal expression and activity of carbonic anhydrase can contribute to increase oxidative stress and to disruption of systemic redox homeostasis which can be associated to possible alterations on vulnerable neurons such as spiral ganglion neurons and consequent cellular degeneration. We therefore evaluated systemic oxidative stress and cellular stress response in patients suffering from Meniere's disease (MD) and in age-matched healthy subjects. Systemic oxidative stress was estimated by measuring protein oxidation, such as protein carbonyls (PC) and 4-hydroxynonenal (HNE) in lymphocytes of MD patients, as well as ultraweak luminescence (UCL) as end-stable products of lipid oxidation in MD plasma and lymphocytes, as compared to age-matched controls, whereas heat shock proteins Hsp70 and thioredoxin (Trx) expression were measured in lymphocytes to evaluate the systemic cellular stress response. Increased levels of PC (P < 0.01) and HNE (P < 0.05) have been found in lymphocytes from MD patients with respect to control group. This was paralleled by a significant induction of Hsp70, and a decreased expression of Trx (P < 0.01), whereas a significant decrease in both plasma and lymphocyte ratio reduced glutathione GSH) vs. oxidized glutathione (GSSG) (P < 0.05) were also observed. In conclusion, patients affected by MD are under condition of systemic oxidative stress and the induction of vitagenes Hsp70 is a maintained response in counteracting the intracellular pro-oxidant status generated by decreased content of GSH as well as expression of Trx. The search for novel and more potent inducers of vitagenes will facilitate the development of pharmacological strategies to increase the intrinsic capacity of vulnerable ganglion cells to maximize antidegenerative mechanisms, such as stress response and thus cytoprotection.

Acoustic analysis of voice in Parkinson's disease: a systematic review of voice disability and meta-analysis of studies. / Análisis acústico de la voz en la enfermedad de Parkinson: revisión sistemática de la discapacidad vocal y metaanálisis de estudios.

AIM: To systematically review all the literature, focusing on instrumental quantitative assessment of voice in patients with Parkinson's disease (PD). Furthermore, a meta-analysis was performed to identify the main characteristics of voice disturbances in PD. PATIENTS AND METHODS: Literature searches with the keywords «Parkinson¼ and «voice¼ were conducted in PubMed, EMBASE, Cochrane Library and Web of Science. Main inclusion criteria were: clinically confirmed PD and instrumented measurement of voice parameters with acoustic analysis of voice. RESULTS: Fourteen publications met the inclusion criteria and were included in the meta-analysis. The data within the meta-analysis revealed that several voice parameters including jitter, shimmer and fundamental frequency variation presented significant variations between patients with EP and healthy controls. Significant variations of fundamental frequency, maximum phonation time, harmonic to noise ratio, standard deviation of fundamental frequency were observed, but with a high heterogeneity between the studies. On the other hand, significant variations of noise to harmonic ratio, s/z ratio, variation of amplitude were not observed. CONCLUSION: Acoustic analysis of voice, using an electronic system, allows the identification of changes in voice parameters for predicting the worsening of disease and for targeting specific intervention. Among the voice parameters, jitter and shimmer significantly increased in patients with PD.

TITLE: Análisis acústico de la voz en la enfermedad de Parkinson: revisión sistemática de la discapacidad vocal y metaanálisis de estudios.Objetivo. Revisar de manera exhaustiva la bibliografía referente a la evaluación instrumental cuantitativa de la voz en pacientes con enfermedad de Parkinson (EP) y realizar un metaanálisis para definir las principales características de los trastornos de la voz en la EP. Pacientes y métodos. Búsquedas bibliográficas con las palabras clave «Parkinson¼ y «voice¼ en PubMed, EMBASE, Cochrane Library y Web of Science. Los principales criterios de aceptación fueron: EP con confirmación clínica y medición instrumentada de los parámetros de la voz mediante análisis acústico. Resultados. Catorce publicaciones cumplieron los criterios de aceptación y se incluyeron en el metaanálisis. De los datos incorporados al metaanálisis, se dedujo que varios parámetros vocales, como el jitter, el shimmer y la variación de la frecuencia fundamental, presentan variaciones significativas en los pacientes con EP frente a los controles sanos. Se hallaron variaciones significativas de la frecuencia fundamental y de su desviación estándar, del tiempo máximo de fonación y de la razón armónicos-ruido, si bien con una alta heterogeneidad entre los estudios. En cambio, no se observaron variaciones sustanciales de la razón ruido-armónicos, en el índice s/z ni en la variación de la amplitud. Conclusión. El análisis acústico de la voz por medio de un sistema electrónico permite detectar los cambios de los parámetros vocales de cara a predecir el empeoramiento de la enfermedad y elegir una intervención específica. Entre dichos parámetros, el jitter y el shimmer aumentaron significativamente en los pacientes con EP.

Hexamethylene bisacetamide inhibits malignant phenotype in T-ALL cell lines.

T acute lymphoblastic leukemia cell lines treated with hexamethylene bisacetamide (HMBA) undergo a delay in cell cycle progression and increase susceptibility to apoptosis, although they never overcome the differentiation block. In accordance with changes in cell cycle and apoptosis, transitory p53 pathway activation commonly occurs. Bcl-2 inhibition further favours the pro-apoptotic effect of HMBA. Notch1 expression is down regulated by reduction of its transcription level. Accordingly, Notch1 protein and transcriptional activity were affected. Even if HMBA generally reduces Notch1 level in T acute lymphoblastic leukemia (T-ALL) cell lines, this does not commonly influence the biological response; in fact all the analysed cell lines, except CEM cells, display no biological effect following DAPT-induced Notch inhibition.

Notch pathway promotes ovarian cancer growth and migration via CXCR4/SDF1α chemokine system.

Ovarian cancer is the most deadly gynecological malignancy. Understanding the molecular pathogenesis of ovarian cancer is critical to provide new targeted therapeutic strategies. Recent evidence supports a role for Notch in ovarian cancer progression and associates its dysregulation to poor overall survival. Similarly, CXCR4/SDF1α signalling correlates with ovarian cancer progression and metastasis. Recent findings indicate that Notch promotes CXCR4/SDF1α signalling and its effect on cell growth and migration; nonetheless, up to now, the association between Notch and CXCR4/SDFα in ovarian cancer has not been reported. Thereby, the aim of this study was to investigate if Notch and CXCR4/SDF1α cooperate in determining ovarian cancer growth, survival and migration. To address this issue, Notch signalling was inhibited by using γ-secretase inhibitors, or upregulated by forcing of Notch1 expression in ovarian cancer cell lines. Our results indicated that Notch activity influenced tumour cell growth and survival and positively regulated CXCR4 and SDF1α expression. CXCR4/SDF1α signalling mediated the effect of Notch pathway on ovarian cancer cell growth and SDF1α-driven migration. Additionally, for the first time, we demonstrated that Notch signalling activation can be detected in ovarian cancer specimens by immunohistochemistry analysis of the Notch transcriptional target, HES6 and is positively correlated with high expression levels of CXCR4 and SDF1α. Our results demonstrate that Notch affects ovarian cancer cell biology through the modulation of CXCR4/SDF1α signalling and suggest that Notch inhibition may be a rationale therapeutic approach to hamper ovarian cancer progression mediated by the CXCR4/SDF1α axis.

Identification of the 5' end of the gene encoding a human insulin-responsive glucose transporter.

The 5' end of a gene (GLT4) encoding a human insulin-responsive glucose transporter was isolated from a human lambda Fix genomic library and sequenced. The human sequence, as compared to the mouse GLT4 promoter [Kaestner et al., Proc. Natl. Acad. Sci. USA 87 (1990) 251-255], revealed an overall homology of 81%. Putative transcription controlling sequences were identified.

Leiomyoma of tunica albuginea of testis.

Leiomyoma is an uncommon lesion which may originate anywhere within the genitourinary system where smooth muscle is present. The third case of leiomyoma of the testicular tunica albuginea is reported, and other reports of genitourinary leiomyomas are reviewed.

Computer sequence analysis of human highly conserved zinc finger modules.

We defined a sub-family of zinc finger proteins by computer analyses and comparisons of five new finger domains against protein databases. This subclass of the cysteine-cysteine/histidine-histidine motif shows additional well conserved amino acid patterns and belongs to the human kox and gli-Kruppel gene family, sharing also the same stretches of regulatory zinc finger-containing proteins of mouse and Xenopus. We particularly describe ZF6 cDNA which contains the most interesting sequence, encoding a putative multi-domain regulatory protein.

Developmental venous anomaly responsible for hemifacial spasm.

Hemifacial spasm (HFS) is a facial movement disorder characterized by involuntary, unilateral and intermittent contractions of the facial muscles. It is one of the syndromes related to neurovascular conflict, first described by Jannetta et al. in 1979. Typically, HFS is due to pulsatile compression by the anterior inferior cerebellar artery. We describe a rare case of left developmental venous anomaly in a 59-year-old man referred to us with a six-month history of left-sided HFS. We performed an MR study of the brain and cerebellopontine angles, which demonstrated a compression of the ipsilateral facial nerve by the developmental venous anomaly.

Traumatic labyrinthine concussion in a patient with sensorineural hearing loss.

Blunt head trauma without any temporal bone fracture or longitudinal temporal bone fracture, with an associated fracture of the labyrinth may cause labyrinthine injury with sensor neural hearing loss and vertigo because of a concussive injury to the membranous labyrinth. Sudden sensory neural hearing loss is relatively frequent. In most cases, the etiology is not discovered. One of the possible causes for sudden deafness is inner labyrinth bleeding or concussion, which were difficult to diagnose before the advent of magnetic resonance imaging. Vertigo without a demonstrable fracture may also be the result of labyrinthine concussion, cupololithiasis and perilymphatic fistula. We describe the clinical case of a patient with acute traumatic hearing loss and vertigo, without skull base fracture detected on computed tomography. Magnetic resonance study was also performed. We have integrated the discussion with features that allow the differential diagnosis from other similar conditions.

Notch-directed microenvironment reprogramming in myeloma: a single path to multiple outcomes.

Multiple myeloma is a deadly hematopoietic malignancy. Despite therapeutic advances such as autologous stem cell transplantation and novel chemotherapeutics, multiple myeloma remains incurable. Multiple myeloma cell localization in the bone marrow and the cross-talk with the bone niche trigger dramatic alterations in the bone marrow microenvironment critical for tumor progression, resistance to therapies and osteolytic bone destruction. It does not surprise that the molecular bases of such fatal interaction are under examination as source of novel potential pharmacological targets. Among these, the Notch family of receptors and ligands has gained growing interest in the recent years because of their early deregulation in multiple myeloma and their ability to affect multiple features of the disease, including tumor cell growth, drug resistance, angiogenesis and bone lesions. This review will explore the evidences of Notch deregulation in multiple myeloma, the state of the art of the currently known roles of its signaling in the fatal interaction between multiple myeloma cells, extracellular matrix and cells in the bone marrow stroma. Finally, we will present recent findings concerning the arguments for or against a therapy addressed to Notch signaling inhibition in the cure of multiple myeloma.

Vascular cerebral anomalies associated with Septo-Optic Dysplasia. A case report.

We describe a case of Septo-Optic Dysplasia (SOD) characterized by the presence of anomalous cerebral vessels. In our young patient the classical features of SOD were associated with vascular anomalies including absence of the vein of Galen, right Rosenthal vein leading to the superior petrosal sinus, and anomalous origin of the anterior choroidal arteries. These findings have never been associated with SOD in the literature but their revelation supports the hypothesis of a vascular disruption as a possible cause of the SOD.

Anti-Notch treatment prevents multiple myeloma cells localization to the bone marrow via the chemokine system CXCR4/SDF-1.

Multiple myeloma (MM) is a deadly hematopoietic malignancy characterized by proliferation of malignant plasma cells in the bone marrow (BM) and bone disease. Interactions between myeloma and BM cells facilitate tumor progression and resistance to therapies. CXCR4 and its ligand Stromal cell-derived factor-1 (SDF-1) have a primary role in this process and are associated with poor prognosis. The Notch pathway is active in myeloma cells, resulting in increased proliferation, resistance to apoptosis and osteolytic activity. We hypothesized that the CXCR4/SDF-1 axis mediates the effects of Notch signals in myeloma cells. Here we show that Notch positively controls CXCR4/SDF-1 expression and functions in myeloma cell lines, and that forced CXCR4 activation partially rescues tumor cells from the outcomes of Notch inhibition. Additionally, we provide evidences that Notch blocking in vivo significantly reduces BM infiltration by human myeloma cells in mouse xenografts. This is the first evidence that a Notch-targeted approach effectively prevents MM cell migration, proliferation and resistance to apoptosis by reducing CXCR4 and SDF-1 levels.

Spontaneous ruptured cavernous aneurysm treated by stenting and embolization in a young patient. A case report and literature review.

We describe a case of endovascular management of a ruptured aneurysm of the intracavernous portion of the left internal carotid artery with sphenoid extension. The exclusive use of coils to embolize the aneurysm in acute and young patients offers the advantage of avoiding both pre-implant antiplatelet therapy and long-term anticoagulant therapy required after stent or vascular plug placement, but it is complicated by the non-negligible risk of recurrence. Indeed, the only secure method to treat ruptured aneurysms of the intracavernous portion of the internal carotid artery is to use coils in the first stage to stop the haemorrhage without antiplatelet therapy and to use stents in the second narrow stage to prevent revascularization.

An occult spinal neurenteric cyst associated with congenital hemivertebrae. A case report.

We describe a case of an occult spinal neurenteric cyst associated with congenital hemivertebrae. Different intraspinal anomalies, such as neurenteric cysts (representing 0.3 to 0.5 % of all spinal tumors) have been reported in association with congenital hemivertebrae. Indeed, although CT is the best examination to study vertebral anomalies, MRI should be performed in order to exclude a more complex dysraphic condition.

Guillain-barré syndrome associated with acute onset bilateral facial nerve palsies. A case report and literature review.

Guillain-Barré syndrome is a post infectious, immune-mediated disease with cranial nerve involvement observed in 45-75% of patients. Bilateral facial nerve palsy is rather uncommon and occurs in 0.3% to 2% of all facial palsies. We describe a rare case of a 29-year-old man with bilateral facial palsy caused by a Guillain-Barré syndrome with an unusual onset and progression of neurological symptoms. Neuroradiological findings in our patient are described and compared with data from literature on bilateral facial palsies to make differential diagnosis easier for neuroradiologists.

Advanced ossification of the posterior longitudinal ligament in a mildly symptomatic patient. A case report and literature review.

We describe the imaging findings of a man who developed neurologic symptoms due to ossification of the posterior longitudinal ligament with narrowing of the spinal canal and compression of the spinal cord. CT study allowed a detailed evaluation of the stenosis and the extension of the ossification while MRI gave an excellent visualization of the spinal lesions caused by spinal cord compression by the mass. The neurological status of patients with ossification of the posterior longitudinal ligament depends on many factors such as the degree of spinal canal stenosis, life style, accidental mechanical stress and trauma.

An orbital lymphoma involving the pterygopalatine and infratemporal fossae. A case report.

Lymphoma is the most common malignant orbital tumor. We describe the imaging features of diffuse orbital follicular lymphoma with extension into the pterygopalatine fossa and infratemporal fossa without bony infiltration.