In vitro cell models merging circadian rhythms and brain waves for personalized neuromedicine

New evidence is emerging about the dynamics of interaction between circadian rhythms and brain waves, whose coordination occurs through the entrainment process. The so-called “oscillopathies” or dysfunctions in synchronization of neuronal oscillation in key brain networks lead to the onset of neurodegenerative diseases. A typical example of alteration is insomnia, a risk factor for the oscillopathies, increasingly widespread worldwide. Recently, synchronization of circadian rhythms in cell cultures has allowed an improvement in the physiological relevance of responses to stimuli. Furthermore, brain organoids and neurons cultured in microfluidic systems are the latest frontiers for in vitro reproduction of rhythmic electrical signals. In this review, the combination of these in vitro experimental approaches is proposed as suitable for a more direct investigation on the common mechanisms and neurophysiological substrates underlying brain waves and circadian oscillations, and useful to evaluate the effects of “oscillotherapeutic” drugs for personalized neuromedicine

A conservative treatment for eosinophilic cystitis

Introduction: Eosinophilic cystitis is a rare condition which causes common symptoms and may mimic other conditions. Eosinophilic cystitis has several causes such as hypereosinophilic syndrome, inflammatory diseases, neoplasia, parasites or fungal infection, IgE-related diseases, Drug Reaction and Eosinophilia and Systemic Symptoms (DRESS) syndrome, or Churg-Strauss syndrome. Therefore, differential diagnosis is difficult. Case presentation: We report the case of a middle-aged man affected by eosinophilic cystitis with persistent hematuria and other peculiar symptoms that may be brought back to hypereosinophilic crisis. Conclusion: Conservative approach is preferred, avoiding radical cystectomy rather than corticosteroid, antihistaminic and second line therapy. Hyperbaric therapy is an innovative approach for severe relapsing gross hematuria without specific literature and should be studied for further indications

Validity Evidence of the Z-Test-SC for Use With Children

No Brasil, há uma escassez de instrumentos para avaliar a dinâmica afetiva e cognitiva de crianças, sendo necessário investir em pesquisas que busquem evidências de validade de técnicas de avaliação para esse público. O Teste de Zulliger no Sistema Compreensivo (Zulliger-SC) é um instrumento que avalia o modo de apreensão da realidade, afetos, auto-percepção, relacionamento interpessoal e funcionamento cognitivo, sendo indicado para uso com crianças, embora sejam escassos os estudos que demonstrem sua validade. Buscou-se contribuir para preencher essa lacuna, comparando os desempenhos de crianças em diferentes etapas do desenvolvimento. Participaram da pesquisa 103 crianças de 6 e 12 anos, estudantes de escolas públicas do interior do estado de São Paulo, que responderam ao instrumento individualmente, na própria escola. O Zulliger-SC diferenciou os participantes de modo coerente ao esperado teoricamente para suas idades, contribuindo com evidências de validade de uso do Zulliger-SC com crianças.En Brasil, hay relativa falta de herramientas para evaluar la dinámica afectiva y cognitiva de niños, siendo necesario invertir en investigaciones que buscan evidencias de validez de algunas técnicas para esa población. El Zulliger - Sistema Integrado (Zulliger-SI) es un instrumento que evalúa el modo de percibir la realidad, los afectos, la autopercepción, la relación interpersonal y funcionamiento cognitivo y puede ser utilizado con niños, pero hay pocos estudios con ese propósito en Brasil. Por lo tanto, el objetivo fue contribuir en este campo, comparándose las respuestas de niños con distintas edades. Participaran 103 niños de 6 e 12 años, estudiantes de escuelas públicas en el estado de São Paulo, que respondieron al test individualmente en la propia escuela. El Zulliger-SC ha diferenciado los niños consistentemente a lo esperado teóricamente para las edades, contribuyendo para validez de su uso con niños.In Brazil, there is a lack of tools to assess the children's affective and cognitive dynamics and investments are needed in research that seeks evidence of validity of some assessment tools for that public. The Zulliger test in the Comprehensive System (Zulliger-SC) evaluates the adequacy of reality perception, affects, self-perception, interpersonal relationship and cognitive processing and can be used with children, although there are few studies with this purpose in Brazil. Thus, the aim was to contribute in this field, comparing the performances in different stages of development. The participants were 103 children aged 6 and 12 years old, students from public schools in the state of São Paulo, who answered the test individually in the schools. The Zulliger-SC distinguished the children consistently with what is theoretically expected for their age, bringing some evidence of the Zulliger's validity with children

A multistate epidemic outbreak of Salmonella Goldcoast infection in humans, June 2009 to March 2010: the investigation in Italy.

After an urgent inquiry into a suspected international outbreak of Salmonella Goldcoast infection was launched by Hungary in October 2009 a nation-wide multidisciplinary investigation was carried out in Italy. The aims were to verify whether the higher than expected number of cases of S. Goldcoast infection that had occurred in Italy in the previous months were linked to the outbreak in Hungary and to determine their origin. Between June 2009 and March 2010, 79 confirmed cases of S. Goldcoast infection were identified. Of these, 17 were part of three different point-source outbreaks probably associated with the consumption of salami. Eating salami was also reported by 20 of the 39 sporadic cases that could be interviewed. Fifteen strains of S. Goldcoast isolated from the cases were typed by pulsed-field gel electrophoresis. They shared more than 90% homology with the Hungarian epidemic strain and were also highly similar to S. Goldcoast strains that had been isolated in Italy from pigs and pork-containing food items in 2009 and 2010. Although the origin of the outbreak and the common source linking the Hungarian and the Italian cases could not be definitively identified, our results suggest a possible zoonotic connection of the outbreak cases with the pork production chain

Psychiatric Disorders and Oxidative Injury: Antioxidant Effects of Zolpidem Therapy disclosed In Silico

Zolpidem (N,N-Dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide) is a well-known drug for the treatment of sleeping disorders. Recent literature reports on positive effects of zolpidem therapy on improving renal damage after cisplatin and on reducing akinesia without sleep induction. This has been ascribed to the antioxidant and neuroprotective capacity of this molecule, and tentatively explained according to a generic structural similarity between zolpidem and melatonin. In this work, we investigate in silico the antioxidant potential of zolpidem as scavenger of five ROSs, acting via hydrogen atom transfer (HAT) mechanism; computational methodologies based on density functional theory are employed. For completeness, the analysis is extended to six metabolites. Thermodynamic and kinetic results disclose that indeed zolpidem is an efficient radical scavenger, similarly to melatonin and Trolox, supporting the biomedical evidence that the antioxidant potential of zolpidem therapy may have a beneficial effect against oxidative injury, which is emerging as an important etiopathogenesis in numerous severe diseases, including psychiatric disorders

Guida alle macrofite acquatiche del Friuli Venezia Giulia I - Piante vascolari

La Direttiva Quadro sulle Acque (2000/60/CE), recepita in Italia dal DL. 152/2006, ha introdotto lo studio delle macrofite acquatiche nella valutazione dello stato ecologico delle acque interne, basato sui criteri tecnici del DM 260/2011. Per i corsi d'acqua è previsto l'uso dell'Indice Biologique Macrophytique en Rivière IBMR (AFNOR, 2003), per i laghi degli indici MTIspecies e MacroIMMI (CNR-ISE, 2009). La certificazione di qualità delle analisi biologiche richiede strumenti conoscitivi adeguati: la creazione di chiavi informatizzate è una tappa fondamentale. Questa guida è stata sviluppata dal Dipartimento di Scienze della Vita dell'Università di Trieste e da ARPA Friuli Venezia Giulia come supporto all'identificazione della flora acquatica regionale. Risulta dalla condivisione delle conoscenze dell'ateneo giuliano con l'esperienza dei tecnici ARPA FVG nell'ambito delle attività di biomonitoraggio per il Piano Regionale di Tutela delle Acque. Le macrofite acquatiche comprendono vegetali molto diversi: alghe macroscopicamente visibili, muschi, epatiche e piante vascolari, a cui è dedicata questa guida. L'elenco floristico comprende taxa tipici di ambienti lotici e lentici, creato in fasi successive. Una prima lista deriva dal confronto tra la quella utilizzata per il calcolo dell'IBMR e la lista delle macrofite acquatiche dei corsi d'acqua italiani pubblicata da ENEA (RT/2009/23/ENEA). La successiva comparazione tra i dati dell'Atlante Corologico del Friuli Venezia Giulia (Poldini 2002) ed una lista risultante da rilievi condotti nel 2009-2010 da ARPA FVG, hanno portato all'elenco di 244 taxa inclusi in questa guida. La suddivisione in Famiglie segue Angiosperm Phylogeny Group III (2009)

Effects of Microencapsulated Ferulic Acid or Its Prodrug Methyl Ferulate on Neuroinflammation Induced by Muramyl Dipeptide

Ferulic acid (Fer) is known for its antioxidant and anti-inflammatory activities, which are possibly useful against neurodegenerative diseases. Despite the ability of Fer to permeate the brain, its fast elimination from the body does not allow its therapeutic use to be optimized. The present study proposes the preparation and characterization of tristearin- or stearic acid-based solid lipid microparticles (SLMs) as sustained delivery and targeting systems for Fer. The microparticles were produced by conventional hot emulsion techniques. The synthesis of the methyl ester of Fer (Fer-Me) allowed its encapsulation in the SLMs to increase. Fer-Me was hydrolyzed to Fer in rat whole blood and liver homogenate, evidencing its prodrug behavior. Furthermore, Fer-Me displayed antioxidant and anti-inflammatory properties. The amount of encapsulated Fer-Me was 0.719 +/- 0.005% or 1.507 +/- 0.014% in tristearin or stearic acid SLMs, respectively. The tristearin SLMs were able to control the prodrug release, while the stearic acid SLMs induced a significant increase of its dissolution rate in water. Jointly, the present results suggest that the tristearin SLMs loaded with Fer-Me could be a potential formulation against peripheral neuropathic pain; conversely, the stearic acid SLMs could be useful for Fer-Me uptake in the brain after nasal administration of the formulation

Targeted activation of the SHP-1/PP2A signaling axis elicits apoptosis of chronic lymphocytic leukemia cells

Lyn, a member of the Src family of kinases, is a key factor in the dys-regulation of survival and apoptotic pathways of malignant B cells in chronic lymphocytic leukemia. One of the effects of Lyn's action is spatial and functional segregation of the tyrosine phosphatase SHP-1 into two pools, one beneath the plasma membrane in an active state promoting pro-survival signals, the other in the cytosol in an inhibited conformation and unable to counter the elevated level of cytosolic tyrosine phosphorylation. We herein show that SHP-1 activity can be elicited directly by nintedanib, an agent also known as a triple angiokinase inhibitor, circumventing the phospho-S591-dependent inhibition of the phosphatase, leading to the dephosphorylation of pro-apoptotic players such as procaspase-8 and serine/threonine phosphatase 2A, eventually triggering apoptosis. Furthermore, the activation of PP2A by using MP07-66, a novel FTY720 analog, stimulated SHP-1 activity via dephosphorylation of phospho-S591, which unveiled the existence of a positive feedback signaling loop involving the two phosphatases. In addition to providing further insights into the molecular basis of this disease, our findings indicate that the PP2A/SHP-1 axis may emerge as an attractive, novel target for the development of alternative strategies in the treatment of chronic lymphocytic leukemia

A new case report of severe mucopolysaccharidosis type VII: diagnosis, treatment with haematopoietic cell transplantation and prenatal diagnosis in a second pregnancy

A new patient with severe mucopolysaccharidosis (MPS) type VII is reported. Non-immune hydrops fetalis (NIHF) was diagnosed during pregnancy. At birth, he showed generalized hydrops and dysmorphic features typical of MPS. Many diagnoses were excluded before reaching the diagnosis of MPS VII at 8 months of life. During the first year of life he had frequent respiratory infections associated with restrictive and obstructive bronchopneumopathy and underwent three surgical interventions: decompression of the spinal cord at the craniocervical junction, bilateral inguinal hernia, and bilateral clubfoot. At 14 months of life he underwent successful haematopoietic cell transplantation (HCT). During the following 10 months, his bronchopneumopathy progressively worsened, needing chronic pharmacological treatment and O2 administration. The patient died of respiratory insufficiency during a respiratory syncytial virus infection at 25 months of age. Molecular analysis showed the homozygous variant c.1617C > T, leading to the synonymous mutation p.Ser539=. This caused aberrant splicing with partial skipping of exon 10 (r.1616_1653del38) and complete skipping of exon 9 (r.1392_1476del85; r.1616_1653del38). No transcript of normal size was evident. The parents were both confirmed to be carriers. In a subsequent pregnancy, a prenatal diagnosis showed an affected fetus. Ultrasound examination before abortion showed NIHF. The skin and placenta examination by electron microscopy showed foamy intracytoplasmic vacuoles with a weakly electron-dense substrate. MPS VII is a very rare disease but it is possible that some cases go undiagnosed for several reasons, including that MPS VII, and other lysosomal storage diseases, are not included in the work-up for NIHF in many institutions, and the presence of anasarca at birth may be confounding for the recognition of the typical facial characteristics of the disease. This is the eighth patient affected by MPS VII who has undergone HCT. It is not possible to draw conclusions about the efficacy of HCT in MPS VII. Treatment with enzyme replacement is now available and will probably be beneficial for the patients who have a milder form with no or little cognitive involvement. Increased awareness among clinicians is needed for prompt diagnosis and to offer the correct treatment as early as possible

West Nile virus transmission with human cases in Italy, August - September 2009.

In 2009, to date 16 human cases of West Nile neuroinvasive disease (WNND) have been reported in Italy, in three regions: Veneto, Emilia-Romagna and Lombardia. The number of cases is higher compared with last year when nine cases were identified (eight cases of WNND and one case of West Nile fever) and the geographical distribution indicates spread from east to west