Programmable (proSA®) vs. fixed (SHUNTASSISTANT®) gravitational valves in pediatric patients with hydrocephalus: a 16-year retrospective single-center comparative study with biomechanical analysis.

PURPOSE: In pediatric hydrocephalus (HC) treatment, programmable gravitational valves offer greater flexibility to manage overdrainage during children's growth. However, it remains unclear whether these devices provide better outcomes rather than their precursors. The study assessed the benefit from programmability of gravitational valve, i.e., programmable-SHUNTASSISTANT (proSA®) vs. SHUNTASSISTANT® (SA®). METHODS: Clinical records and imaging of pediatric patients with hydrocephalus of non-tumoral etiology treated with fixed (SA®) or programmable (proSA®) gravitational valves between January 2006 and January 2022 were analyzed in a retrospective single-center study. Valve survival was compared in relation to age and etiology. Lately explanted valves received biomechanical analysis. RESULTS: A total of 391 gravitational valves (254 SA® and 137 proSA®) were inserted in 244 patients (n = 134 males). One hundred thirty-three SA® (52.4%) and 67 proSA® (48.9%) were explanted during a follow-up of 81.1 ± 46.3 months. Valve survival rate at 1 and 5 years with proSA® was 87.6% and 60.6% compared to 81.9% and 58.7% with SA®, with mean survival time 56.4 ± 35.01 and 51.4 ± 43.0 months, respectively (P = 0.245). Age < 2 years at implantation correlated with significantly lower valve survival rates (P < 0.001), while HC etiology showed no significant impact. Overdrainage alone accounted for more SA® revisions (39.8% vs. 3.1%, P < 0.001), while dysfunctions of the adjustment system represented the first cause of valve replacement in proSA® cohort (45.3%). The biomechanical analysis performed on 41 proSA® and 31 SA® showed deposits on the valve's internal surface in 97.6% and 90.3% of cases. CONCLUSION: Our comparative study between proSA® and SA® valves in pediatric HC demonstrated that both valves showed similar survival rates, regardless of etiology but only with young age at implantation. The programmability may be beneficial in preventing sequelae of chronic overdrainage but does not reduce need for valve revision and proSA® valve should be considered in selected cases in growing children older than 2 years.

The applicability of fixed and adjustable gravitational shunt valves in two different clinical settings.

BACKGROUND: Gravitational shunt valves and most recently the adjustable proSA® gravitational valve have been designed to counteract overdrainage and thereby improving clinical outcome. So far, the applicability in a broader mix of hydrocephalus patients is unrevealed. The aim of this study was to evaluate the utility of gravitational valves in two different clinical settings. METHODS: This retrospective double-center cohort study was enabled by two different shunt management policies. At Rigshospitalet, patients with a complicated shunt history receiving a proGAV® and proSA® shunt system during surgical revision were included, and clinical outcome in the follow-up periods before and after was compared. At Aarhus University Hospital, a combination of a proGAV® and a fixed (SA®) or adjustable (proSA®) gravitational valve was used in all shunt procedures. Clinical outcome in a 2-year follow-up period was compared to a cohort receiving non-gravitational valves in the period before the transition to gravitational valves. RESULTS: Twenty-two patients were included at Rigshospitalet. Mean follow-up time before and after proGAV® and proSA® implantation was 2.3 and 1.5 years, respectively. In each patient, roughly two surgical revisions (p 0.031) and two hospitalizations (p 0.009) were avoided each year after proGAV® and proSA® implantation. At Aarhus University Hospital, 90 patients with non-gravitational valves and 98 patients with gravitational valves were included. Changes in clinical outcome parameters and shunt survivals were either stable or statistically insignificant. CONCLUSIONS: Gravitational valves are safe and useful in clinical practice and represent an equivalent alternative as a first-line shunt valve in a broad mix of patients, while proSA® valves should be considered for complex shunt patients.

From fixed-pressure paediGAV to programmable proGAV/proSA serial valves for pediatric hydrocephalus within the 1st year of life: a technical single-center analysis.

OBJECTIVE: Programmable valves have gained increasing popularity in the complex treatment of pediatric hydrocephalus. Over the last decade, adjustable serial valves have gradually replaced fixed-pressure valves in the authors' department. The present study investigates this development by analyzing shunt- and valve-related outcomes for this vulnerable population. METHODS: A retrospective analysis of all shunting procedures between January 2009 and January 2021 in children younger than 1 year of age was performed at the authors' single-center institution. Postoperative complications and surgical revisions were set as outcome parameters. Shunt and valve survival rates were evaluated. Statistical analysis compared children who underwent implantation of the Miethke proGAV/proSA programmable serial valves with those who underwent implantation of the fixed-pressure Miethke paediGAV system. RESULTS: Eighty-five procedures were evaluated. The paediGAV system was implanted in 39 cases and the proGAV/proSA in 46 cases. The mean ± SD follow-up was 247.7 ± 140 weeks. In 2009 and 2010, paediGAV valves were used exclusively, but by 2019, the use of proGAV/proSA had evolved into the first-line therapy. The paediGAV system was significantly more often revised (p < 0.05). The main indication for revision was proximal occlusion, with or without impairment to the valve. The valve and shunt survival rates of proGAV/proSA were significantly prolonged (p < 0.05). The surgery-free valve survival of proGAV/proSA was 90% after 1 year and 63% after 6 years. There were no overdrainage-related revisions of proGAV/proSA valves. CONCLUSIONS: Favorable shunt and valve survival validates the increasing use of programmable proGAV/proSA serial valves in this delicate population. Potential benefits in postoperative treatment should be addressed in prospective multicenter studies.

Framework for multi-criteria assessment of classification models for the purposes of credit scoring.

The main dilemma in the case of classification tasks is to find-from among many combinations of methods, techniques and values of their parameters-such a structure of the classifier model that could achieve the best accuracy and efficiency. The aim of the article is to develop and practically verify a framework for multi-criteria evaluation of classification models for the purposes of credit scoring. The framework is based on the Multi-Criteria Decision Making (MCDM) method called PROSA (PROMETHEE for Sustainability Analysis), which brought added value to the modelling process, allowing the assessment of classifiers to include the consistency of the results obtained on the training set and the validation set, and the consistency of the classification results obtained for the data acquired in different time periods. The study considered two aggregation scenarios of TSC (Time periods, Sub-criteria, Criteria) and SCT (Sub-criteria, Criteria, Time periods), in which very similar results were obtained for the evaluation of classification models. The leading positions in the ranking were taken by borrower classification models using logistic regression and a small number of predictive variables. The obtained rankings were compared to the assessments of the expert team, which turned out to be very similar.

Introducing a simple model system for binding studies of known and novel inhibitors of AMPK: a therapeutic target for prostate cancer.

Prostate cancer (PC) is one of the leading cancers in men, raising a serious health issue worldwide. Due to lack of suitable biomarker, their inhibitors and the platform for testing those inhibitors result in poor prognosis of PC. AMP-activated protein kinase (AMPK) is a highly conserved protein kinase found in eukaryotes that is involved in growth and development, and also acts as a therapeutic target for PC. The aim of the present study is to identify novel potent inhibitors of AMPK and propose a simple cellular model system for understanding its biology. Structural modelling and MD simulations were performed to construct and refine the 3D models of Dictyostelium and human AMPK. Binding mechanisms of different drug compounds were studied by performing molecular docking, molecular dynamics and MM-PBSA methods. Two novel drugs were isolated having higher binding affinity over the known drugs and hydrophobic forces that played a key role during protein-ligand interactions. The study also explored the simple cellular model system for drug screening and understanding the biology of a therapeutic target by performing in vitro experiments.

Design and screening of syringic acid analogues as BAX activators-An in silico approach to discover "BH3 mimetics".

Although BAX, which is a molecular hit squad that incentive apoptosis was found to be an attractive emerging target for anticancer agents. The molecular mechanism of small molecules/peptides involved in the BAX activation was remain unknown. The present focus of the study is to identification and development of novel molecules which are precisely activates BAX mediated apoptosis. In this process we identified some syringic acid analogues associated with the BAX hydrophobic groove by a virtual-screen approach. Results from the docking studies revealed that, SA1, SA9, SA10, SA14 and SA21 analogues have shown good interaction with BAX trigger site, of which SA10 and SA14 bound specifically with Lys21 at α1 helix of BAX, a critical residue involved in BAX activation. All docking calculations of SA analogues were compared with clinically tested BH3 mimetics. In this entire in silico study, SA analogous have performed an ideal binding interactions with BAX compared to BH3 mimetics. Further, in silico point mutation of BAX-Lys21 to Glu21 resulted in structural change in BAX and showed reduced binding energy and hydrogen bond interactions of the selected ligands. Based on these findings, we propose that virtual screening and mutation analysis of BAX is found to be the critical advance method towards the discovery of novel anticancer therapeutics.

Development of an in vitro Bioassay for Recombinant Human Erythropoietin (rHuEPO) Based on Proliferative Stimulation of an Erythroid Cell Line and Analysis of Sialic Acid Dependent Microheterogeneity: UT-7 Cell Bioassay.

Determination of biological activity and its comparison with clinical behavior is important in the quality assessment of therapeutic glycoproteins. In vivo studies are usually employed for evaluating bioactivity of these glycomolecules. However, alternative methods are required to simplify the bioassay and avoid ethical issues associated with in vivo studies. Negatively charged sialic acid residues are known to be critical for in vivo bioactivity of rHuEPO. To address this need, we employed the human acute myeloid leukemia cell line UT-7 for the determination of proliferative stimulation induced by rHuEPO. Relative potencies of various intact and sugar-trimmed rHuEPO preparations were estimated using the International Standard for Human r-DNA derived EPO (87/684) as a reference for bioactivity. The cellular response was measured with a multi-channel photometer using a colorimetric microassay, based on the metabolism of the Resazurin sodium by cell viability. For a resourceful probing of physiological features of rHuEPO with significance, we obtained partly or completely desialylated rHuEPO digested by the neuraminidase enzyme without degradation of carbohydrates. Two-fold higher specific activity was shown by asialoerythropoietin in in vitro analysis compared with the sialoerythropoietin. Further, computational studies were also carried out to construct the 3D model of the erythropoietin (EPO) protein structure using standard comparative modeling methods. The quality of the model was validated using Procheck and protein structure analysis (ProSA) server tools. N-glycan units were constructed; moreover, EPO protein was glycosylated at potential glycosylation amino acid residue sites. The method described should be suitable for potency assessments of pharmaceutical formulations of rHuEPO (European Pharmacopeia, 2016).

Dataset generated for Dissection of mechanisms of Trypanothione Reductase and Tryparedoxin Peroxidase through dynamic network analysis and simulations in leishmaniasis.

Leishmaniasis is the second largest parasitic killer disease caused by the protozoan parasite Leishmania, transmitted by the bite of sand flies. It's endemic in the eastern India with 165.4 million populations at risk with the current drug regimen. Three forms of leishmaniasis exist in which cutaneous is the most common form caused by Leishmania major. Trypanothione Reductase (TryR), a flavoprotein oxidoreductase, unique to thiol redox system, is considered as a potential target for chemotherapy for trypanosomatids infection. It is involved in the NADPH dependent reduction of Trypanothione disulphide to Trypanothione. Similarly, is Tryparedoxin Peroxidase (Txnpx), for detoxification of peroxides, an event pivotal for survival of Leishmania in two disparate biological environment. Fe-S plays a major role in regulating redox balance. To check for the closeness between human homologs of these proteins, we have carried the molecular clock analysis followed by molecular modeling of 3D structure of this protein, enabling us to design and test the novel drug like molecules. Molecular clock analysis suggests that human homologs of TryR i.e. Glutathione Reductase and Txnpx respectively are highly diverged in phylogenetic tree, thus, they serve as good candidates for chemotherapy of leishmaniasis. Furthermore, we have done the homology modeling of TryR using template of same protein from Leishmania infantum (PDB ID: 2JK6). This was done using Modeller 9.18 and the resultant models were validated. To inhibit this target, molecular docking was done with various screened inhibitors in which we found Taxifolin acts as common inhibitors for both TryR and Txnpx. We constructed the protein-protein interaction network for the proteins that are involved in the redox metabolism from various Interaction databases and the network was statistically analysed.

The cleaner, the greener? Product sustainability assessment of the biomimetic façade paint Lotusan® in comparison to the conventional façade paint Jumbosil®.

Background: The debate on the question whether biomimetics has a specific potential to contribute to sustainability is discussed among scientists, business leaders, politicians and those responsible for project funding. The objective of this paper is to contribute to this controversial debate by presenting the sustainability assessment of one of the most well-known and most successful biomimetic products: the façade paint Lotusan®. Results: As a first step it has been examined and verified that the façade paint Lotusan® is correctly defined as a biomimetic product. Secondly, Lotusan® has been assessed and compared to a conventional façade paint within the course of a detailed product sustainability assessment (PROSA). For purposes of comparison, the façade paint Jumbosil® was chosen as reference for a conventional paint available on the market. The benefit analysis showed that both paints fulfil equally well the requirements of functional utility. With respect to the symbolic utility, Lotusan® has a particular added aesthetic value by the preservation of the optical quality over the life cycle. Within the social analysis no substantial differences between the two paints could be found regarding the handling and disposal of the final products. Regarding the life-cycle cost, Lotusan® is the more expensive product. However, the higher investment cost for a Lotusan®-based façade painting are more than compensated by the longer life time, resulting in both reduced overall material demand and lower labour cost. In terms of the life-cycle impact assessment, it can be ascertained that substantial differences between the paints arise from the respective service life, which are presented in terms of four scenario analyses. Conclusion: In summary, the biomimetic façade paint Lotusan® has been identified as a cost-effective and at the same time resource-saving product. Based on the underlying data and assumptions it could be demonstrated that Lotusan®-based façade paintings have a comparatively low overall impact on the environment. Summarizing our results, it can be emphasized that Lotusan® is the more favourable product compared to Jumbosil® according to sustainability aspects.

Fernando Pessoa: precursor das inteligências múltiplas / Fernando Pessoa: precursor das inteligencias múltiples / Fernando Pessoa: precursor of multiple intelligences

Este artigo trata das relações passíveis de serem estabelecidas entre a teoria da inteligência e a prosa de Fernando Pessoa. Para tanto, aborda como argumentação e inteligência se relacionam cientificamente e são trabalhadas pelo autor na elaboração de sua obra em prosa. Destaca características peculiares da atividade em prosa em tempos da Geração de Orpheu que fundamentam a apresentação das formas de inteligência no autor, a saber, Inteligência Filosófica, Inteligência Científica e Inteligência Crítica. Na sequência, objetiva discorrer sobre a possibilidade de Pessoa ser um precursor das inteligências múltiplas

This article deals with the relations that can be established between the theory of intelligence and the prose of Fernando Pessoa. To this end, it discusses how argumentation and intelligence are scientifically related and are worked on by the author in the elaboration of his prose work. Addresses peculiar characteristics of prose activity at the time of the Generation of Orpheu, proceeding to the presentation of forms of intelligence, namely, philosophical intelligence, scientific intelligence and critical intelligence. In the sequence, objective deals about the possibility of Pessoa being a precursor of multiple intelligences.

Este artículo trata sobre las relaciones que pueden establecerse entre la teoría de la inteligencia y la prosa de Fernando Pessoa. Com este fin, analiza cómo la argumentación y la inteligencia están cientificamente relacionadas y el autor las trabaja en la elaboración de su trabajo em prosa. Aborda las formas de inteligencia, a saber, inteligencia filosófica, inteligencia científica e inteligencia crítica cómo características peculiares de la actividad en prosa en el momento de lá generación de Orpheu. En la secuencia, trata la possibilidad de Pessoa sea un precursor de inteligencias múltiples.

Literatura, poesia e psicanálise / Literature, poetry and psychoanalysis / Literatura, poesía y psicoanálisis

O autor propõe nesta comunicação aproximar a experiência literária e poética da observação e apreensão da realidade psíquica no trabalho analítico. A partir da entrevista concedida pelo escritor Mia Couto para a Revista Brasileira de Psicanálise, e acrescentando textos de outro autor, Jorge Luis Borges, enfatiza a importância do vértice estético-artístico como fundamento da pesquisa psicanalí-tica. A literatura e os poetas têm muito a nos ensinar, na medida em que o fenômeno mental, hoje, não é mais propriedade da psicanálise, ou melhor, na medida em que a psicanálise é um dos meios de observação e pesquisa da realidade psíquica, da experiência humana.

The author proposes, through this paper, to link literary and poetical experience to the observation and apprehension of the psychic reality in analytical work. Starting withth an interview carried out by this journal with the writer Mia Couto, and adding texts by another author, Jorge Luis Borges, the author emphasizes the importance of the aesthetic-artistic vertex as a foundation of psychoanalytic research. Literature and poets have a lot to teach us, considering that the mental phenomenon, today, is no longer property of psychoanalysis.That is to say, psychoanalysis is one of the vertices of observation and research of psychic reality, of the human experience.

En este artículo el autor propone aproximar la experiencia literaria y poética a la observación y comprensión de la realidad psíquica en el trabajo analítico. A partir de la entrevista concedida por el escritor Mia Couto a la Revista Brasileira de Psicanálise, y añadiendo textos de otro autor, Jorge Luis Borges, enfatiza la importancia del vértice estético-artístico como fundamento de la investigación psicoanalítica. La literatura y los poetas tienen mucho que enseñarnos, en la medida en que el fenómeno mental, hoy en día, dejó de ser una propiedad del psicoanálisis, o mejor, el psicoanálisis es uno de los medios de observación e investigación de la realidad psíquica, de la experiencia humana.

A terceira margem do rio: um diálogo entre poesia (sonho) e prosa (vigília)

O diálogo entre poesia (sonho) e prosa (vigília) nas obras homônimas A terceira margem do rio, permitiu evidenciar os mecanismos deslocamento, condensação e figurabilidade entre as palavras de Caetano Veloso e de João Guimarães Rosa. Nesse sentido, a ideia de uma terceira margem do rio que encerra o indizível, presente em ambas as obras, permite pensar a palavra como representação de coisa, a palavra em sua materialidade que flexibiliza a relação entre significante e significado (água da palavra). Mas é metaforicamente na relação com o pai que se encerram as raízes de toda cadeia associativa. São os desejos inconsciente, submersos no rio, que reagem os operadores e que criam os meandros da rede de associações ora convergentes e ora contraditórias denunciando a presença escondida, disfarçada da(i)lógica do desejo inconsciente(AU)

The dialogue between poetry (dream) and prose (vigil), in the homophonous Works A terceira margem do rio, shows the mechanisms of displicement, consensation and figurability between the words os Caetano Veloso and João Guimarães Rosa. The idea of a third shore of river that contains the unspeakable, found in both woks, allows one to think thing-word the word in is materiality that turns looser the relation between referente and meaning (water of the word). But it is metaphorically in the relation with the father that the roots of the associative chain are found. Unconscious desires, inside the river, conduct operations and create the texture of the web of associations, cometimes converging sometimes conflictiong, denoucing the hidden, disguised presence of the (il)logic the unconscious desire