A novel micro-photogrammetric instrument for visualizing in 3D small objects applied to the quantitative study of the dissolution behavior of a pharmaceutical dosage form

The work presented here proposes an innovative approach to 3D chemical mapping of solid formulations by micro-photogrammetry. We present details of a novel micro-photogrammetry apparatus and the first results for the application of photogrammetry to the dissolution analysis of solid pharmaceutical dosage forms. Unlike other forms of optical imaging, micro-photogrammetry allows a true 3D model to be con-structed that includes direct observation of the sides of the sample rather than only top-down topographic imaging. Volume and structural changes are assessed quantitatively and related to chemical analysis by high performance liquid chromatography (HPLC). The recently introduce method of chemical identifica-tion by dissolution analysis, or chemical imaging by dissolution analysis (CIDA), is employed for the first time to obtain tomographic images of the dissolution process

Effectiveness of cyclosporine and mycophenolate mofetil in a child with refractory evans syndrome

Evans Syndrome is a rare autoimmune disease consisting of hemolytic anemia, thrombocytopenia and/or neutropenia. It may be associated with other autoimmune or lymphoproliferative diseases. Its course can be extremely serious and, rarely, even life-threatening; thus it represents a excellent treatment challenge for the pediatric hematologist. First line treatment consists of steroids and/or immunoglobulin; further therapy with rituximab, vincristine, cyclophosphamide and other immunosuppressive drugs can be considered in unresponsive patients. We describe a baby with refractory Evans Syndrome that was cured by prolonged administration of mycophenolate mofetil and remained disease-free for 4 years after the discontinuation of treatment

La eficacia de las medidas de protección y el derecho a la integridad, en el caso de las víctimas de violencia familiar del distrito de Trujillo, 2022

En la presente investigación, se busca analizar la figura de las medidas de protección dictadas a favor de las víctimas del delito de violencia familiar, la cual se encuentra enfocada en determinar la garantía del derecho a la integridad de este sector de la población en relación a la eficacia de las medidas de protección dictadas por un Juzgado de Familia. El mismo que nos planteamos al haber observado la gran cantidad de reincidencias e incumplimientos de dichas medidas, en donde la única persona que se ve afectada es la víctima; pues esta confía plenamente en la efectividad de la Ley N.º 30364 y su Reglamento; sin embargo, las medidas de protección dictadas a favor de la víctima, no aseguran a plenitud su derecho fundamental a la integridad. Para desarrollar el tema se tuvo como fuente de información distintas bases de datos como Ebsco, Redalyc, Scielo, Google Academy y repositorios institucionales, entre otros, utilizando tesis y libros los cuales contengan las variables utilizadas, posteriormente se realizó una revisión sistemática para determinar ideas esenciales y determinantes al tema que se desarrolla. Por otro lado, con la finalidad de comparar con la realidad problemática, se realizaron entrevistas a especialistas en la materia, así como también se realizó un profundo análisis a la Ley N.º 30364 y su Reglamento.In this investigation, we seek to analyze the figure of the protection measures issued in favor of the victims of the crime of family violence, which is focused on determining the guarantee of the right to integrity of this sector of the population in relation to the effectiveness of the protection measures issued by a Family Court. The same that we consider having observed a large number of recidivism and breaches of said measures, where the only person who is affected is the victim; because this person fully trusts the effectiveness of Law No. 30364 and its Regulations; however, the protection measures issued in favor of the victim don't fully ensure their fundamental right to integrity. To develop this topic, we had as a source of information different databases such as Ebsco, Redalyc, Scielo, Google Academy, and institutional repositories, among others, using theses and books which contain the variables used, later a systematic review was carried out to determine ideas essential and decisive to the theme that is developed. In addition, in order to compare with the problematic reality, interviews were conducted with specialists in this area, as well as an in-depth analysis of Law No. 30364 and its Regulations

Generating glycan variants for biological activity testing by means of parallel experimental design and multivariate analysis

For more than 20 years, the industry has mainly invested in productivity enhancements. Recently, the focus of cell-culture process development began to shift. The modulation of quality attributes of recombinant therapeutic protein has gained substantial interest as demonstrated by the plethora of recent publications describing the effect of cell culture media on post-translational modifications of recombinant proteins1. Focusing on glycosylation, our team has developed a toolbox of media design beyond the commonly known media components and a rational high-throughput experimental design method. We identified and tested a large variety of novel cell culture compatible chemical components in industrial relevant Chinese hamster ovary cell lines (CHO) expressing recombinant antibodies and antibody fusion molecules. The compounds were evaluated in five different parallel 96-DWP fed-batch experiments, considering their mode of biological action. Viable cell density, viability and product titer were monitored and purified supernatants underwent N-glycan analysis by 2AB-UPLC and site-specific glycan-peptide analysis. Multivariate analysis identified the best performing glycosylation modulators, which were confirmed in spin tubes. Intracellular nucleotide and nucleotide sugar levels were analyzed by capillary electrophoresis, the gene expression by next-generation sequencing technologies, and the impact of the generated glycan variants on the biological activity was assessed. Non-targeted metabolite profiling was carried out to build a multivariate model linking metabolites with the glycan fingerprint. The screening experiments in 96-DWP produced a large glycosylation distribution diversity2,3. Subsequent D-optimal quadratic design in shake tubes confirmed the outcome of the selection process and provided a solid basis for sequential process development at a larger scale. The glycosylation profile with respect to the glycosylation specifications was greatly improved in shake tube experiments: 75% of the conditions were equally close or closer to the specifications than the best 25% in 96-deepwell plates. Further enhancement enabled us to generate extreme glycosylation variants, including high mannose, afucosylated, galactosylated as well as sialic acid species of both a mAb and an antibody fusion molecule with three N-glycosylation sites. The glycan variants induced significant responses in the respective in vitro biological activity assays. Moreover, metabolites correlating with time-dependent glycan profiling data were pinpointed and the glycan distribution of an external data set predicted. Our data highlight the great potential of cell culture medium optimization to modulate product quality and show the feasibility of the generation of a wide range of glycan variants suitable for biological activity testing. [1] Brühlmann D, Jordan M, Hemberger J, Sauer M, Stettler M and Broly H, Tailoring recombinant protein quality by rational media design, Biotechnology Progress 2015, 31:615–629. [2] Brühlmann D, Muhr A, Parker R, Vuillemin T, Bucsella B, Torre S, La Neve F, Lembo A, Haas T, Sauer M, Souquet J, Broly H, Hemberger J, Jordan M, Cell culture media supplemented with raffinose reproducibly enhances high mannose glycan formation, Journal of Biotechnology 2017, 252:32-42. [3] Brühlmann D, Sokolov M, Butté A, Sauer M, Hemberger J, Souquet J, Broly H, Jordan M, Parallel experimental design and multivariate analysis provides efficient screening of cell culture media supplements to improve Biosimilar product quality, Biotechnology and Bioengineering 2017, 114(7):1363-1631

Duration of constant rate infusion with diazepam or propofol for canine cluster seizures and status epilepticus

IntroductionConstant rate infusion (CRI) of benzodiazepines or propofol (PPF) is a therapeutic option for cluster seizures (CS) and status epilepticus (SE) in canine patients non-responding to first-line benzodiazepines or non-anesthetics. However, specific indications for optimal duration of CRI are lacking. The aim of this study was to determine the effect of duration of anesthetic CRI on outcome and length of hospital stay in dogs with refractory seizure activity of different etiology.Study designOpen-label non-randomized clinical trial.Materials and methodsSeventy-three client-owned dogs were enrolled. Two groups [experimental (EXP) vs. control (CTRL)] were compared. The EXP group received diazepam (DZP) or PPF CRI for 12 h (±1 h) and the CTRL group received DZP or PPF CRI for 24 h (±1 h) in addition to a standardized emergency treatment protocol identical for both study groups. The historical control group was made up of a population of dogs already reported in a previously published paper by the same authors. Favorable outcome was defined as seizure cessation after CRI, no seizure recurrence, and clinical recovery. Poor outcome was defined as seizure recurrence, death in hospital or no return to acceptable clinical baseline. Univariate statistical analysis was performed.ResultsThe study sample was 73 dogs: 45 (62%) received DZP CRI and 28 (38%) received PPF CRI. The EXP group was 39 dogs (25 DZP CRI and 14 PPF CRI) and the CTRL group 34 dogs (20 DZP CRI and 14 PPF CRI). We found no statistically significant difference in outcomes between the groups. The median length of stay was 56 h (IQR, 40–78) for the ALL EXP group and 58.5 h (IQR, 48–74.5) for the ALL CTRL group (p = 0.8).ConclusionEven though a shorter DZP or PPF CRI duration was not associated with a worse outcome, the study failed to identify a clear superiority of shorter CRI duration on outcome or length of hospital stay in dogs with refractory seizure activity of different etiology

Modeling the Cerebellar Microcircuit: New Strategies for a Long-Standing Issue

The cerebellar microcircuit has been the work bench for theoretical and computational modeling since the beginning of neuroscientific research. The regular neural architecture of the cerebellum inspired different solutions to the long-standing issue of how its circuitry could control motor learning and coordination. Originally, the cerebellar network was modeled using a statistical-topological approach that was later extended by considering the geometrical organization of local microcircuits. However, with the advancement in anatomical and physiological investigations, new discoveries have revealed an unexpected richness of connections, neuronal dynamics and plasticity, calling for a change in modeling strategies, so as to include the multitude of elementary aspects of the network into an integrated and easily updatable computational framework. Recently, biophysically accurate realistic models using a bottom-up strategy accounted for both detailed connectivity and neuronal non-linear membrane dynamics. In this perspective review, we will consider the state of the art and discuss how these initial efforts could be further improved. Moreover, we will consider how embodied neurorobotic models including spiking cerebellar networks could help explaining the role and interplay of distributed forms of plasticity. We envisage that realistic modeling, combined with closed-loop simulations, will help to capture the essence of cerebellar computations and could eventually be applied to neurological diseases and neurorobotic control systems

Axial Spondyloarthritis: Reshape the Future—From the “2022 GISEA International Symposium”

The term “axial spondyloarthritis” (axSpA) refers to a group of chronic rheumatic diseases that predominantly involve the axial skeleton and consist of ankylosing spondylitis, reactive arthritis, arthritis/spondylitis associated with psoriasis (PsA) and arthritis/spondylitis associated with inflammatory bowel diseases (IBD). Moreover, pain is an important and common symptom of axSpA. It may progress to chronic pain, a more complicated bio-psychosocial phenomena, leading to a significant worsening of quality of life. The development of the axSpA inflammatory process is grounded in the complex interaction between genetic (such as HLA B27), epigenetic, and environmental factors associated with a dysregulated immune response. Considering the pivotal contribution of IL-23 and IL-17 in axSpA inflammation, the inhibition of these cytokines has been evaluated as a potential therapeutic strategy. With this context, here we discuss the main pathogenetic mechanisms, therapeutic approaches and the role of pain in axSpA from the 2022 International GISEA/OEG Symposium

Infection in a Geriatric Patient: Do Not Let Your Guard Off!

Tetanus is an infectious disease caused by Clostridium tetani toxin. Although easily preventable through vaccination, over 73,000 new infections and 35,000 deaths due to tetanus occurred worldwide in 2019, with higher rates in countries with healthcare barriers. Here, we present a clinical case of C. tetani infection in an 85-year-old patient. Patient robustness and high functional reserve before infection are favorable predictors of survival for an otherwise fatal disease. However, the patient did not experience any severe complications. Therefore, this report is a strong call for tetanus vaccination