A 75 year old man comes to the pharmacy to pick up the medications n prescribed after a 2 week hospitalization period due to a fall at his habitual residence, with the result of a broken femur. The patient lives in a nursing home where staff prepare his medication in customized dispensing systems. The unique new prescribed drug is paracetamol (1g) only if pain appears and with maximum dose of 3g per day. Tha patient daily consumes:

• Mirtazapine 30 mg
• Escitalopram 15 mg
• Ketazolam 30 mg
• Lorazepam 5 mg
• Dutasteride 0.5 mg
• Omeprazol 20 mg

We note that for their anxious-depressive symptoms he consumes two benzodiazepines at higher than recommended dose for his age along with two antidepressants, one of which has high doses sedative effect (mirtazapine). We do not know how long he has been taken with all these drugs but it refers than more than four months.

Because it is an retrospective evaluation we can not establish a causal relationship of treatment with the fall,  but we may suspect that the fall was triggered by an overdose of benzodiazepines. We get in touch with the doctor of the nursing home e to discuss the case who decides to withdraw ketazolam treatment and subsequently valued reduction in the dose of mirtazapine according to the patient's response.

The elderly population is a special risk group for drug adverse events, due to factors such as changes in pharmacokinetic and pharmacodynamic processes, with frequent presence of multiple pathologies and polypharmacy.
We mus to remember the importance of the review of the dose and duration of treatment with benzodiazepines in the elderly and follow the recommendations of clinical guidelines for selecting those with short or ultrashort BZD of life, at the lowest possible dose for the shortest time.

The atom-quadratic indices are used in this work together with some machine learning techniques that includes: support vector machine, artificial neural network, random forest and k-nearest neighbor. This methodology is used for the development of two quantitative structure-activity relationship (QSAR) studies for the prediction of proteasome inhibition. A first set consisting of active and non-active classes was predicted with model performances above 85% and 80% in training and validation series, respectively. These results provided new approaches on proteasome inhibitor identification encouraged by virtual screenings procedures.

Today, one of the main aims in the pharmaceutical companies is seek new methodologies to understand the biological activity in molecules from the computational point of view. In this sense, understand the traditional tools (3D QSAR) such as the Comparative Molecular Similarity Analysis (CoMSIA) within the quantum chemistry framework, can be relevant.

In this context, the quantification of steric and electrostatic effects on a serie of antimalarials chalcones was performed on the basis of the descriptors from the molecular quantum similarity field and chemical reactivity supported in DFT. The steric and electrostatic effects were studied using scales of convergence quantitative alpha (α) and beta (β), respectively. To deal the problem of relative molecular orientation in the quantum similarity field the Topo-Geometrical Superposition Algorithms (TGSA) was used as molecular alignment method. Finally, a chemical reactivity analysis using global and local descriptors such as chemical hardness, softness, electrophilicity, and Fukui Functions was developed.

The internet aids to promote a new process of data/information transmission that two decades ago simply did not exist. A simple search on the internet provides an answer; new discussion forums often provide answers that would take days or even weeks of research. Nevertheless, some information is still obtained indirectly and relatively time consuming, hence techniques of bank architecture chemical data, query and visualization have been developed constantly. We can find several internet applications to search and predict spectroscopic data, biological activity of ligands, or to predict toxicity of new compounds or pesticides  [1].

Our research group is developing SISTEMAT X web, [2] a tool that manages databases of natural products. Currently, our database has more than 1,100 sesquiterpene lactones and 800 flavonoids with more than four thousand botanical occurrences of the Asteraceae family and approximately 400 alkaloids which represents more than 750 botanical occurrences of the Apocynaceae family and several terpenes of Annonaceae that correspond more than 800 botanical occurrences .

SISTEMAT X is a set of integrated programs and tools that perform cheminformatics tasks that include database management, chemical structure editor, visualization of chemical structures, and prediction of physicochemical properties among others [2]. Most of the components are intuitive and friendly using a graphical interface. In the last year we have migrated applications that use Java interface for JavaScript, since the last is geared to web pages. This software has already been registered by our research group, through Federal University f Paraíba, in “Instituto Nacional de Propriedade Industrial” with number BR 51 2015 000073. The site is running at the address: www.sistematx.ufpb.br. We are developing constantly it, improving existing features such as adding new. All tools are available to the scientific community.

References:

1. Gasteiger, J. 2003. Handbook of Chemoinformatics: From Data to Knowledge, Ed. 4 v. Wiley-VCH. Weinheim.
2. sistematx.ufpb.br

Introduction: It was observed that technology developers expressed a clear interest to design programs that meet the needs of individuals with Autism Spectrum Disorder (ASD). Several authors indicate that any software designed for people with ASD has to include special requirements in the design. Methodology: This research study describes a software for children with ASD named Module ASD and describes the interactive process of design that it was followed. This research focuses on a software development and the design process, based on scientific evidence study, consultation and tests done by specialists, children with ASD and their families. The techniques used to formalize the collection of information from different groups of participants were: observation, interview, group discussions and field book. Results: The ASD Module is the result of the study and it is a free technological application that is made up of a set of virtual keyboards (or adapted interfaces), digital schedules and activities, especially designed and tested by and for children with ASD. The application is included in the In-TIC PC software. The software is available for the Windows operating system and was implemented with the Visual Studio development tool, .NET environment, C# programming language and Windows Form technology. Other materials used for content development were the Interactive Books Multimedia (LIM according to the Spanish acronym) software and the ARASAAC pictograms. Discussion and conclusions: The results show that the digital content can be oriented to promote independence in several daily activities (ADL, education, leisure and social participation). This technology design provides useful information for researchers, developers, social and healthcare professionals and families, with the aim of offering alternatives for children with ASD and facilitating the understanding of daily life.

Mizoroki-Heck reaction constitutes an effective method for the formation of quaternary stereocenters. This reaction has been applied to functionalized 2-alkenylpyrroles as substrates in which the b-elimination is blocked by a methyl substituent. 10,10-Disubstituted pyrrolo[1,2-b]isoquinolines can be obtained using different palladium catalysts and chiral bidentate phosphanes as ligands, although with low enantioselectivities. In some cases, competition between Mizoroki-Heck reaction and C-H direct arylation reaction on the pyrrole nucleus has also been observed for this type of polyfunctionalized substrates. Finally, we have shown that quaternary stereocenters can be generated using chiral phosphane ligands as (R)-BINAP, through a cascade polyene cyclization. This procedure has been successfully applied to the construction of tetracyclic framework of Lycorine class of Amaryllidaceae alkaloids

The diastereoselective Mizoroki-Heck reaction of N-benzylpyrrolidines that incorporate a protected allylic alcohol moiety allows the synthesis of enantiomerically pure pyrrolo[1,2-b]isoquinolines, generating a tertiary stereocenter. The best results were obtained with the use of bulky phosphanes, as P(o-Tol)₃. When a good leaving group, such as pivaloyl is used as a protecting group, the trans-10-vinyl substituted pyrroloisoquinoline (10S,10aS)-2a is obtained as the major diastereoisomer in moderate yield. On the other hand, when the allylic alcohol is protected as a silyl ether, the protected alcohol is retained, obtaining an enol ether, whichafter deprotection and reduction leads to the trans-10-hydroxymethyl substituted pyrrolisoquinoline (10S,10aS)-5, in enantiomerically pure form, with complete diastereoselectivity.

The α,β-unsaturated ketones known as benzalacetones are an interesting class of compounds frequently used as key intermediates in organic synthesis. Due to their conjugated system, benzalacetone and derivatives have been described as radical scavengers with potential antioxidant properties. We report here a simple and direct method to prepare functionalized α,β-unsaturated ketones via a microwaves activated Claisen-Schmidt reaction. The experimental protocol developed selectively produces benzalacetones without self-condensation product in very short reaction times and good yields. Interested in the biological properties of benzalacetones, we also studied the antioxidant potential of these compounds using an in silico study based on the DPPH• radical scavenging ability. The built mathematical model was based on the 0-3D DRAGON molecular descriptors and the artificial neural networks technique showing a correlation coefficient for the training set (R²) = 0.71, an external correlation coefficient (Q²_ext) = 0.65 . Unfortunately, the results obtained in the in-silico study revealed that synthesized benzalacetones have no antioxidant activity. The predicted results have been confirmed experimentally by an in vitro assay of DPPH• scavenging capacity.

Different research projects around the world are trying to emulate the human brain. They employ diverse types of computational models: digital models, analog models and hybrid models. This communication includes a summary of some main projects, as well as future trends in this subject. It is focused on various works that look for advanced progress in Neuroscience and still others which seek new discoveries in Computer Science (neuromorphic hardware, machine learning techniques). In addition, given the proven importance of glial cells in information processing, the importance of considering astrocytes into the brain computational models is pointed out.

Malaria is one of the leading causes of death by infectious disease worldwide. The widespread of resistance to the current antimalarial drugs makes urgent the search and discovery of new targets and new drugs. A potential target for the development of new antimalarial drugs is deoxyuridine triphosphatase (dUTPase), and it has been validated for Escherichia coli, Saccharomyces cerevisiae and Mycobacterium smegmatis. This enzyme plays an important role in maintaining the balance between 2'-deoxyuridine 5'-triphosphate (dUTP) and 2'- deoxythymidine 5'-triphosphate (dTTP), in order to avoid the erroneous incorporation uracil in the DNA tape. In this study, we developed robust conformation-independent fragment-based quantitative structure–activity (QSAR) and structure–selectivity relationship (QSSR) models for a series of β-branched acyclic nucleotides inhibitors of Plasmodium and human dUTPase, aiming to design new anti-malarial agents. The Hologram QSAR and QSSR models generated showed good robustness and external predictability, and is capable of predict affinity and selectivity of untested compounds inside the applicability domain. Therefore, the generated models can be used in virtual screening campaigns in the search of new potent and selective PfdUTPase inhibitors.