Dopamine genes and migraine

Migraine is a common chronic disorder with an etiology still mostly unknown. Several neurotransmitters such as dopamine and serotonin are considered to be involved in the pathogenesis of the disease and the study of their systems is crucial in the understanding of migraine. Dopaminergic receptors are variously represented in human CNS and periphery. The hypothesis that a hypersensitivity of the dopaminergic system may have a role in migraine is based on clinical and genetic data. Genetic data are represented by association studies using dopaminergic genes as candidate genes which show that the D2 receptor gene appears to be involved in the pathogenesis of migraine

Foraminiferal biotopes in a shallow continental shelf environment: Esperance Bay (southwestern Australia)

The Great Australian Bight is a large carbonate cold water environment located on the central and western portions of the southern Australia. Seagrasses (Posidonia sp.) and macroalgae benthic habitats are widely distributed in the shallow water environment of southern Australia, contributing to the carbonate factory. This study investigated the distribution of modern benthic foraminiferal assemblages in the microtidal wave-dominated inner-shelf of Esperance Bay (southwestern Australia), that lies on the western margin of the Great Australian Bight. Benthic foraminifera were taxonomically identified and biotic parameters (species richness, density, Fisher-α index, Shannon–Weaver index, dominance) were calculated. Multivariate analyses (Hierarchical Cluster Analysis, Principal Component Analysis) were performed to understand foraminiferal distribution in the context of environmental conditions. Four main Foraminiferal assemblages have been recognized: (I) a nearshore assemblage of dense seagrass meadow, dominated by Lamellodiscorbis dimidiatus, Elphidium craticulatum, Elphidium crispum, Cibicidoides lobatulus, II) a second assemblage associated with unvegetated seabed (approximately 30 m depth) with Lamellodiscorbis dimidiatus, Elphidium crispum, Quinqueloculina disparilis, III) a third assemblage in the central sector of the bay, characterized by a discontinuous and mixed seagrass-algae coverage with Lamellodiscorbis dimidiatus, Elphidium crispum, Elphidium macellum, Cibicides refulgens, and Quinqueloculina poeyana, and IV) an epiphytic assemblage of transitional zone from the coastline to the upper limit of a mixed seagrass-algae meadow, dominated by Elphidium crispum, Chrysalidinella dimorpha, Planulinoides biconcava, Planoglabratella opercularis, Rugobolivinella elegans. The spatial distribution of the four assemblages appears closely related to sediment texture, seagrass cover and depth, but it is also influenced by the shoreface morphology and the hydrodynamic energy. The understanding of the ecological parameters that influence benthic foraminiferal distribution, composition and assemblage structure within seagrass meadows is useful for paleoecological and paleoenvironmental interpretations

Distribution of HLA-DPB1, -DQB1 -DQA1 alleles among Sardinian celiac patients.

The Sardinian population in many aspects differs from other Caucasoid populations, particularly for its degree of homogeneity. For this reason we have studied 50 adult Sardinian patients with celiac disease (CD) and 50 control healthy Sardinian individuals by RFLP analysis and by extensive oligotyping for 17 HLA-DPB 1, 8-DQB I and 9-DQA 1 alleles, and established their -DPB I alleles and -DQB I -DQA I genotypes. The heterodimer HLA-DQB 1 *0201/-DQA 1 *0501, present in 96% of our patients, is strongly associated with CD susceptibility, confirming published reports. On the other hand we found in 11 of 50 probands (22%) the presence of the allele -DQB 1 *05021 DQA1*0102. This genotype is extremely rare in other Caucasian populations and appears to confer limited protection in CD Sardinian patients

Diabetes insipidus secondary to nivolumab-induced neurohypophysitis and pituitary metastasis

A 62-year-old patient with metastatic hypopharyngeal carcinoma underwent treatment with nivolumab, following which he developed symptoms suggestive of diabetes insipidus. Nivolumab was stopped and therapy with methylprednisolone was started. During corticosteroid therapy, the patient presented himself in poor health condition with fungal infection and glycemic decompensation. Methylprednisolone dose was tapered off, leading to the resolution of mycosis and the restoration of glycemic compensation, nevertheless polyuria and polydipsia persisted. Increase in urine osmolarity after desmopressin administration was made diagnosing central diabetes insipidus as a possibility. The neuroradiological data by pituitary MRI scan with gadolinium was compatible with coexistence of metastatic localization and infundibuloneurohypophysitis secondary to therapy with nivolumab. To define the exact etiology of the pituitary pathology, histological confirmation would have been necessary; however, unfortunately, it was not possible. In the absence of histological confirmation, we believe it is likely that both pathologies coexisted

Clinical strategies to aim an adequate safety profile for patients and effective training for surgical residents: The laparoscopic cholecystectomy model

Background Training programs for resident surgeons represent a challenge for the mentoring activity. The aim of the present study is to investigate the impact of our training program for laparoscopic cholecystectomy on patient's safety and on the modulation of the residents' exposure to clinical scenario with different grades of complexity. Material and methods This is a retrospective study based on a clinical series of laparoscopic cholecystectomy performed in a teaching hospital. Study population was grouped according to the expertise of the attending primary operator among resident surgeons. Four groups were identified: consultant (C), senior resident (SR); intermediate level resident (IR); junior resident (JR). The intraoperative and postoperative outcomes were confronted to evaluate the patient's safety profile. Results 447 patients were submitted to LC: 96 cases were operated by a C, 200 by SR, 112 by IR and 39 by JR. The mean operative time was the longest for the JR group. A statistically higher rate of conversion to open approach was registered in C and IR groups in comparison to JR and SR groups. However, in C and IR groups, patients had worse ASA score, higher BMI and more frequent past history of previous abdominal surgery, cholecystitis or pancreatitis. Overall, it was not registered any statistically significant difference among the groups in terms of length of hospital stay and prevalence of major postoperative complications. Conclusion Applying an educational model based on both graduated levels of responsibility and modulated grade of clinical complexity can guarantee an high safety profile

Surface Periodic Poling in Lithium Niobate and Lithium Tantalate

Periodic Poling of Lithium Niobate crystals (PPLN) by means of electric field has revealed the best technique for finely tailoring PPLN structures and parameters, which play a central role in many current researches in the field of nonlinear integrated optics. Besides the most studied technique of bulk poling, recently a novel technique where domain inversion occurs just in a surface layer using photoresist or silica masks has been devised and studied. This surface periodic poling (SPP) approach is best suited when light is confined in a thin surface guiding layer or stripe, as in the case of optical waveguide devices. Also, we found that SPP respect to bulk poling offers two orders of magnitude reduction on the scale of periodicity, so that even nanostructures can be obtained provided an high resolution holographic mask writing technique is adopted. We were able to demonstrate 200 nm domain size, and also good compatibility with alpha-phase proton exchange channel waveguide fabrication. Our first experiments on Lithium Tantalate have also shown that the SPP technology appears to be applicable to this crystal (SPPLT), whose properties can allow to overcome limitations such as optical damage or UV absorption still present in PPLN devices. Finally, the issue of SPP compatibility with proton exchange waveguide fabrication will be addresse

A2B Adenosine Receptors and Sphingosine 1-Phosphate Signaling Cross-Talk in Oligodendrogliogenesis

Oligodendrocyte-formed myelin sheaths allow fast synaptic transmission in the brain. Impairments in the process of myelination, or demyelinating insults, might cause chronic diseases such as multiple sclerosis (MS). Under physiological conditions, remyelination is an ongoing process throughout adult life consisting in the differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes (OLs). During pathological events, this process fails due to unfavorable environment. Adenosine and sphingosine kinase/sphingosine 1-phosphate signaling axes (SphK/S1P) play important roles in remyelination processes. Remarkably, fingolimod (FTY720), a sphingosine analog recently approved for MS treatment, plays important roles in OPC maturation. We recently demonstrated that the selective stimulation of A(2)(B) adenosine receptors (A(2)(B)Rs) inhibit OPC differentiation in vitro and reduce voltage-dependent outward K(+) currents (I(K)) necessary to OPC maturation, whereas specific SphK1 or SphK2 inhibition exerts the opposite effect. During OPC differentiation A(2)(B)R expression increases, this effect being prevented by SphK1/2 blockade. Furthermore, selective silencing of A(2)(B)R in OPC cultures prompts maturation and, intriguingly, enhances the expression of S1P lyase, the enzyme responsible for irreversible S1P catabolism. Finally, the existence of an interplay between SphK1/S1P pathway and A(2)(B)Rs in OPCs was confirmed since acute stimulation of A(2)(B)Rs activates SphK1 by increasing its phosphorylation. Here the role of A(2)(B)R and SphK/S1P signaling during oligodendrogenesis is reviewed in detail, with the purpose to shed new light on the interaction between A(2)(B)Rs and S1P signaling, as eventual innovative targets for the treatment of demyelinating disorders

A2b adenosine receptors: When outsiders may become an attractive target to treat brain ischemia or demyelination

Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here, we review data in the literature describing A2BR-mediated effects in models of cerebral ischemia obtained in vivo by the occlusion of the middle cerebral artery (MCAo) or in vitro by oxygen-glucose deprivation (OGD) in hippocampal slices. Adenosine plays an apparently contradictory role in this receptor subtype depending on whether it is activated on neuro-glial cells or peripheral blood vessels and/or inflammatory cells after ischemia. Indeed, A2BRs participate in the early glutamate-mediated excitotoxicity responsible for neuronal and synaptic loss in the CA1 hippocampus. On the contrary, later after ischemia, the same receptors have a protective role in tissue damage and functional impairments, reducing inflammatory cell infiltration and neuroinflammation by central and/or peripheral mechanisms. Of note, demyelination following brain ischemia, or autoimmune neuroinflammatory reactions, are also profoundly affected by A2BRs since they are expressed by oligodendroglia where their activation inhibits cell maturation and expression of myelin-related proteins. In conclusion, data in the literature indicate the A2BRs as putative therapeutic targets for the still unmet treatment of stroke or demyelinating diseases