Inhibition of phosphoinositide 3-kinase/protein kinase B signaling hampers the vasopressin-dependent stimulation of myogenic differentiation

Arginine-vasopressin (AVP) promotes muscle differentiation, hypertrophy, and regeneration through the combined activation of the calcineurin and Calcium/Calmodulin-dependent Protein Kinase (CaMK) pathways. The AVP system is impaired in several neuromuscular diseases, suggesting that AVP may act as a physiological factor in skeletal muscle. Since the Phosphoinositide 3-kinases/Protein Kinase B/mammalian Target Of Rapamycin (PI3K/Akt/mTOR) signaling plays a significant role in regulating muscle mass, we evaluated its role in the AVP myogenic effect. In L6 cells AKT1 expression was knocked down, and the AVP-dependent expression of mTOR and Forkhead box O3 (FoxO) was analyzed by Western blotting. The effect of the PI3K inhibitor LY294002 was evaluated by cellular and molecular techniques. Akt knockdown hampered the AVP-dependent mTOR expression while increased the levels of FoxO transcription factor. LY294002 treatment inhibited the AVP-dependent expression of Myocyte Enhancer Factor-2 (MEF2) and myogenin and prevented the nuclear translocation of MEF2. LY294002 also repressed the AVP-dependent nuclear export of histone deacetylase 4 (HDAC4) interfering with the formation of multifactorial complexes on the myogenin promoter. We demonstrate that the PI3K/Akt pathway is essential for the full myogenic effect of AVP and that, by targeting this pathway, one may highlight novel strategies to counteract muscle wasting in aging or neuromuscular disorders

Portal vein thrombosis and Budd-Chiari syndrome as onset of Polycythaemia Vera.

Budd-Chiari syndrome may be defined as a heterogeneous group of vascular disorders characterized by obstruction of hepatic venous return to the level of hepatic venules, supra-hepatic veins, inferior vena cava or right atrium. The main cause of this syndrome is represented by myeloproliferative diseases and, in particular, by polycythemia vera. The latter may cause multiple splanchnic thrombosis, including portal vein thrombosis, particularly important for its clinical outcomes (ascites, collateral vessels genesis, etc.). We report 2 cases of a Budd-Chiari syndrome induced by polycythemia vera characterized by an abnormal clinical onset, both as regards subjects’ age (29 and 39 years old, respectively) and set of symptoms, signs and laboratory data. After a complete clinical, instrumental and genetic diagnosis, the patients were treated with combined therapy, using acetylsalicylic acid and hydroxyurea. The therapy proved successful and patients are still in follow up in our institution. Polycythemia vera should be suspected in patients affected with portal vein thrombosis and Budd-Chiari syndrome even if its clinical onset might be unusual. Every effort should be made to make a correct and early diagnosis in order to start appropriate therapy as soon as possible and to prevent patients from useless diagnostic and therapeutic treatments

A multinational consensus on dysphagia in Parkinson's disease: screening, diagnosis and prognostic value

Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD. Objective: To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients. Methods: A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. Results: Eighty-five papers were used to inform the Panel’s statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions. Conclusions: The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD

Consensus on the treatment of dysphagia in Parkinson's disease

BACKGROUND: Dysphagia is common in Parkinson's disease (PD). The effects of antiparkinsonian drugs on dysphagia are controversial. Several treatments for dysphagia are available but there is no consensus on their efficacy in PD. OBJECTIVE: To conduct a systematic review of the literature and to define consensus statements on the treatment of dysphagia in PD and related nutritional management. METHODS: A multinational group of experts in the field of neurogenic dysphagia and/or Parkinson's disease conducted a systematic evaluation of the literature and reported the results according to PRISMA guidelines. The evidence from the retrieved studies was analyzed and discussed in a consensus conference organized in Pavia, Italy, and the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. RESULTS: The literature review retrieved 64 papers on treatment and nutrition of patients with PD and dysphagia, mainly of Class IV quality. Based on the literature and expert opinion in cases where the evidence was limited or lacking, 26 statements were developed. CONCLUSIONS: The statements developed by the Consensus panel provide a guidance for a multi-disciplinary treatment of dysphagia in patients with PD, involving neurologists, otorhinolaryngologists, gastroenterologists, phoniatricians, speech-language pathologists, dieticians, and clinical nutritionists

Effects of Therapy in Oropharyngeal Dysphagia by Speech and Language Therapists: A Systematic Review

Medical and paramedical treatments should be evaluated according to current standards of evidence-based medicine. Evaluation of therapy in oropharyngeal dysphagia fits into this growing interest. A systematic review is given of the literature on the effects of therapy in oropharyngeal dysphagia carried out by speech therapists. Thus, the review excludes reports of surgical or pharmacological treatments. The literature search was performed using the electronic databases PubMed and Embase. All available inclusion dates up to November 2008 were used. The search was limited to English, German, French, Spanish, and Dutch publications. MESH terms were supplemented by using free-text words (for the period after January 2005). Fifty-nine studies were included. In general, statistically significant positive therapy effects were found. However, the number of papers was rather small. Moreover, diverse methodological problems were found in many of these studies. For most studies, the conclusions could not be generalized; comparison was hindered by the range of diagnoses, types of therapies, and evaluation techniques. Many questions remain about the effects of therapy in oropharyngeal dysphagia as performed by speech and language therapists. Although some positive significant outcome studies have been published, further research based on randomized controlled trials is needed

RUOLO DELL'ECOGRAFIA CON MEZZO DI CONTRASTO NELLA MALATTIA DI CROHN

RUOLO DELL'ECOGRAFIA CON MEZZO DI CONTRASTO NELLA MALATTIA DI CROHN Nome del convegno: 41° Congresso Nazionale SIRM Luogo del convegno: Palermo Anno del convegno: MAGGIO 2004 Dettaglio tipologia d'Ateneo: 10 - Abstract di Comunicazioni o Poster di Congressi nazionali pubblicati (anche on line

An unexpected demographic regime: The western necropolis of the Greek colony of Himera (Sicily, Italy) (550-409 BCE)

We present the results of a paleodemographic assessment of 2865 graves excavated in the western necropolis of the ancient Greek colony of Himera in Sicily. Himera provides an outstanding opportunity to understand the demographic dynamics of Ancient Sicily as it was abandoned and never repopulated, thus offering a completely intact record. Not only has a remarkably large sample been collected and is currently under study, but historical sources allow to precisely date the years in which the city’s necropolises were used. Children under the age of 5 were typically buried in pots, meaning that the number of children who died at ages 0 and 1–4 can be reliably estimated. Such data on child death is very rare in paleodemographic studies. Thanks to these exceptional characteristics, together with the application of demographic methods already employed in previous studies (Barbiera et al., 2021) and a comparison of our results with other contemporary Greek necropolises, we can discern a plausible mortality regime for Himera. Our analyses reveal that in the western necropolis of Himera (mid-6th to late 5th century BC) the mortality of children and young people was relatively low, and likely compensated by a more pronounced mortality of adults. Life expectancy at birth was plausibly between 25 and 30 years of age. These fndings are further supported by data from the Greek cities of Metaponto and Akraiphia, as well as preliminary results for the eastern necropolis of Himera (late-7th to late 6th century BC)

Dynamic Fast Imaging Employing Steady State Acquisition Magnetic Resonance Imaging of the Vocal Tract in One Overtone Male Singer: Our Preliminary Experience

Aims: To demonstrate physiological changing of vocal tract's structures during overtone singing with commercial magnetic resonance imaging (MRI) Fast Imaging Employing Steady State Acquisition (FIESTA) dynamic sequence. Methods and Materials: A 1.5 T MRI with a 16 channel head-and-neck coil and a FIESTA sequence were used. A temporal resolution of 0.155 sec (7 image/s). A single professional singer was studied. The MR acquisition is made while the singer performed a predetermined singing sequence. Three different overtone singing techniques were examined (L-technique, J-technique, and NG technique) and one effect (Ezengileer) applied to L-technique. For each overtone technique we evaluated MRI movement of lips, tongue, velopharyngeal closure, and relationship among tongue and pharyngeal posterior wall/soft palate. To cancel the noise over-imposed, the dynamic MRI was subsequently dubbed in studio with the audio of the preset overtone sing. Dubbed MR images were analyzed with an Overtone Analyzer Software and different sound frequencies were identified and pointed out as colored lines. Results: This study shows that different overtone techniques are related to a specific conformation of tongue, lips, soft and hard palate and motion's relation changing between them. Only a correct conformation of vocal tract's structure allows resonance and so to hear desired fundamental and harmonic pitch in overtone singing. Conclusion: The preliminary data of our study demonstrates that FIESTA dynamic MRI sequence can be used to depict changing of position of vocal tract's structure in overtone singing techniques with a good temporal and anatomic resolution