Effect of sintering temperature on properties of transparent YSZ-ceramics prepared by spark plasma sintering

Transparent yttria-stabilized zirconia (YSZ) ceramics were sintered with the spark plasma sintering (SPS) method at different temperatures. The influence of sintering temperature (1200-1400°С) on the ceramics microstructure and mechanical properties was investigated and discussed

Search for peripheral biomarkers in patients with psychotic bipolar disorder vs controls: a proteomic approach.

Background. Data on neurobiological mechanisms underlying mood disorders are elusive, aetiology of such states is multifactorial including genetic predisposition and environmental factors. Diagnosis is currently made solely on interview-based methodology. Biological markers which could improve the current classification and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. We describe here the preliminary data on a proteomic analysis from peripheral lymphocytes of patients with acutely psychotic bipolar disorder, compared with a group of subjects with depression and no personal or family history of psychosis and a group of demographically matched healthy controls. Methods. Patients were sampled and evaluated by means of SCID-I, PANSS, YMRS, HAM-A, HAM-D. Lymphocytes have been separated and Two-dimensional electrophoresis (2-DE) was carried out on protein extracts. Analysis was performed using Progenesis Same Spot software. Results. 12 acutely psychotic patients with bipolar disorder have been recruited as well as 8 patients with mild to moderate depression. Acutely psychotic patients were on a PRN (as required) medication regimen since 1-2 days before blood taking. Patients with depression were on a regular therapy with SSRIs (2 patients also mood stabilizers). 12 healthy volunteers matched for age, gender and exclusion criteria were also recruited. 2-DE shows significant differences in protein pattern between the three groups. PCA underlies a clear separation between controls and patients groups, with a t1 value for the first component of 63,96%. T- Test for independent samples shows that 48 protein spots were found to be differentially expressed in patients compared to controls (p<0.001), with an increase in expression for most spots in patients and a decrease in expression for 6 spots. Comparison between patients groups shows 6 protein spots differentially expressed with statistical significance (p <0.001). Conclusions. Preliminary analyses on a small sample show significant differences in protein pattern for both patients groups compared with healthy control. Patients with acutely psychotic bipolar disorder and patients with depression may have some distinct peripheral biomarkers as well as common patterns of protein expression. Proteins are currently under identification using Mass Spectrometry and this could shed light into neurobiological mechanisms involved in the pathogenesis of the disorders

Sustainable Reimbursements: Towards a Unified Framework for Pricing Drugs with Significant Uncertainties

Recent political events have thrust the bulk negotiation of drug prices by Medicare and Medicaid back into the spotlight. Yet, even if politically feasible, there is no clear framework for negotiating prices of new drugs with uncertain target populations—for example, due to imprecise estimates or off-label use—or uncertain clinical effects—for example, due to heterogeneous patient response. We create such a framework using two-price programs developed in the economics of procurement literature. This framework delivers new payment strategies, and unifying them with theoretical advances in pharmaceutical reimbursement like capitation and value-based pricing. Two-price programs substantially reduce uncertainty for both payers and pharmaceutical companies, while still creating financial incentives for those companies that innovate and create value for patients

The European Medicines Agency's strategies to meet the challenges of Alzheimer disease

Regulatory agencies have a key role in facilitating the development of new drugs for Alzheimer disease, particularly given the challenges associated with early intervention. Here, we highlight the strategies of the European Medicines Agency to help address such challenges

За кадры. 1979. № 64 (2214)

Быть впереди, вести за собой / В. И. КрутовИх сила - в дружбеТребуется помощь / Г. ГалкинаСлагаемые активности / Т. ЕвгеньеваНовый состав бюро ВЛКСМ молодых научных сотрудниковДоводить дело - до конца / Г. ПротасоваПерспективые коллектива / Р. ГорскаяО ГДР на ее языке / М. Малашонок, Н. Бегичева, Е. ЯкушевЛюбимое занятие / Г. ГригорьеваКому нужна эта этика? / М. Этштейн"Гея" и круг ее друзей / Г. Венделев

Drug development for Autism Spectrum Disorder (ASD): Progress, challenges, and future directions

In 2017, facing lack of progress and failures encountered in targeted drug development for Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders, the ISCTM with the ECNP created the ASD Working Group charged to identify barriers to progress and recommending research strategies for the field to gain traction. Working Group international academic, regulatory and industry representatives held multiple in-person meetings, teleconferences, and subgroup communications to gather a wide range of perspectives on lessons learned from extant studies, current challenges, and paths for fundamental advances in ASD therapeutics. This overview delineates the barriers identified, and outlines major goals for next generation biomedical intervention development in ASD. Current challenges for ASD research are many: heterogeneity, lack of validated biomarkers, need for improved endpoints, prioritizing molecular targets, comorbidities, and more. The Working Group emphasized cautious but unwavering optimism for therapeutic progress for ASD core features given advances in the basic neuroscience of ASD and related disorders. Leveraging genetic data, intermediate phenotypes, digital phenotyping, big database discovery, refined endpoints, and earlier intervention, the prospects for breakthrough treatments are substantial. Recommendations include new priorities for expanded research funding to overcome challenges in translational clinical ASD therapeutic research

Search for peripheral biomarkers in patients affected by acutely psychotic bipolar disorder: a proteomic approach

Data on neurobiological mechanisms underlying mood disorders are elusive; the aetiology of such states is multifactorial, including genetic predisposition and environmental factors. Diagnosis is currently being made only on an interview-based methodology. Biological markers, which could improve the current classification, and in perspective, stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. We describe here a comparative proteomic analysis of peripheral lymphocytes from patients affected by acute psychotic bipolar disorder (PBD) (n = 15), major depressive episode (MDE) with no personal or family history of psychosis (n = 11), and a group of demographically matched healthy controls (HC) (n = 15). All patients were evaluated by means of Structured Clinical Interview for DSM-IV-Patient version (SCID-I-P), Positive and Negative Symptoms Scale (PANSS), Young Mania Rating Scale (YMRS), Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D-17) questionnaires. Blood lymphocytes were obtained by gradient separation, and 2-DE was carried out on protein extracts. Significant differences in protein patterns among the three groups were observed. Thirty-six protein spots were found to be differentially expressed in patients compared to controls, which collapsed into 25 different proteins after mass spectrometry identification. Twenty-one of these proteins failed to discriminate between PBD and MDE, suggesting common signatures for these disorders. Nevertheless, after the western blot validation only two of the remaining proteins, namely LIM and SH3 domain protein1, and short-chain specific acyl-CoA dehydrogenase mitochondrial protein, resulted in being significantly upregulated in PBD samples suggesting additional mechanisms that could be associated with the psychotic features of bipolar disorder