Ion-ion association is lost by linearizing the Poisson-Boltzmann equation when deriving the Debye-Hückel equation.

In this work, we demonstrate how the ion association constant can be attributed to the difference between the full Poisson-Boltzmann equation and its linearized version in very dilute solutions. We follow a pragmatic approach first by deriving an analytical approximated solution to the Poisson-Boltzmann equation, then calculating its respective Helmholtz free energy and activity coefficient, and then finally comparing it to the contribution from the mass action law principle. The final result is the Ebeling association constant. We conclude that electrostatic ion-ion interaction models miss the ion association contribution naturally introduced in higher-order electrostatic theories. We also demonstrate how the negative deviations from the Debye-Hückel limiting law can be physically attributed to the ion association phenomenon.

Investigation of the Limits of the Linearized Poisson-Boltzmann Equation.

This work presents a comparison between a numerical solution of the Poisson-Boltzmann equation and the analytical solution of its linearized version through the Debye-Hückel equations considering both size-dissimilar and common ion diameters approaches. In order to verify the limits in which the linearized Poisson-Boltzmann equation is capable to satisfactorily reproduce the nonlinear version of Poisson-Boltzmann, we calculate mean ionic activity coefficients for different types of electrolytes as various temperatures. The divergence between the linearized and full Poisson-Boltzmann equations is higher for lower molalities, and both solutions tend to converge toward higher molalities. For electrolytes of lower valencies (1:1, 1:2, 2:1, and 1:3) and higher distances of closest approach, the full version of the Debye-Hückel equation is capable of representing the activity coefficients with a low divergence from the nonlinear Poisson-Boltzmann. The size-dissimilar full version of Debye-Hückel represents a clear improvement over the extended version that uses only common ion diameters when compared to the numerical solution of the Poisson-Boltzmann equation. We have derived a salt-specific index (Θ) to gradually classify electrolytes in order of increasing influence of nonlinear ion-ion interactions, which differentiate the Debye-Hückel equations from the nonlinear Poisson-Boltzmann equation.

Cereus jamacaru D.C. (Mandacaru): a Promising Native Brazilian Fruit as a Source of Nutrients and Bioactives Derived from its Pulp and Skin.

Aiming the valorisation of the fruit of Cereus jamacaru D.C. (mandacaru), from the Caatinga biome, the physicochemical and nutritional parameters, total phenolic content and antioxidant capacity of its raw pulp and skin were evaluated. Extracts of the lyophilised pulp (PE) and skin (SE) of this fruit were also characterised for their antioxidant capacity parameters, phenolic compounds and for the semi-quantitative elemental analysis of minerals. From the total carbohydrates of the pulp (13.43 g/100 g, in the fresh basis), 79% was composed by total dietary fibre and, from this fraction, 89% was insoluble dietary fibre. The total antioxidant capacity of the raw skin was about 1.5-fold higher than that of the raw pulp, while the improvement of phenolic content in the lyophilised PE and SE was by 5- and 36-folds, respectively, compared with their respective raw samples (fresh basis). The lyophilised SE had the higher antioxidant capacity, requiring only 3.79 g to scavenge 1 g of DPPH radicals. Frequencies of functional groups assessed through the FT-IR spectrum corroborates with the presence of phenolic compounds in the samples. Potassium was the predominant mineral in both PE and SE. These results indicate that mandacaru, currently consumed only locally, can be an important source of nutrients and antioxidants for the general population and also for industrial use.

Are all-atom any better than united-atom force fields for the description of liquid properties of alkanes?

Alkanes are a fundamental part in empirical force fields (FF) not only due to their technological relevance, but also due to the prevalence of alkane moieties in organic molecules, e.g., compounds containing a saturated carbon chain. Therefore, a good description of alkane interactions is crucial for determining the quality of a FF. In this study, the performance of 12 empirical force fields (FF) was evaluated in the context of reproducing liquid properties of alkanes. More specifically, n-octane was chosen as a reference compound since it is a liquid in a broad temperature range and it has numerous experimental data for thermodynamic, transport, and structural properties, as well as for their temperature dependencies. A normalized root-mean-square deviation (NRMSD) analysis was used to rank the force fields in their ability to reproduce the experimental data. Five out of the six best force fields considered were united-atom models. The GROMOS force field showed the smallest deviation in terms of NRMSD, followed by TRAPPE-EH, NERD, CHARMM-UA, TRAPPE-UA, and OPLS-UA. This overall better performance of the united-atom force fields indicates that complexity does not always bring quality.

Pioneering Study on Rhopalurus crassicauda Scorpion Venom: Isolation and Characterization of the Major Toxin and Hyaluronidase.

Scorpionism is responsible for most accidents involving venomous animals in Brazil, which leads to severe symptoms that can evolve to death. Scorpion venoms consist of complexes cocktails, including peptides, proteins, and non-protein compounds, making separation and purification procedures extremely difficult and time-consuming. Scorpion toxins target different biological systems and can be used in basic science, for clinical, and biotechnological applications. This study is the first to explore the venom content of the unexplored scorpion species Rhopalurus crassicauda, which inhabits exclusively the northernmost state of Brazil, named Roraima, and southern region of Guyana. Here, we pioneer the fractionation of the R. crassicauda venom and isolated and characterized a novel scorpion beta-neurotoxin, designated Rc1, and a monomeric hyaluronidase. R. crassicauda venom and Rc1 (6,882 Da) demonstrated pro-inflammatory activities in vitro and a nociceptive response in vivo. Moreover, Rc1 toxin showed specificity for activating Nav1.4, Nav1.6, and BgNav1 voltage-gated ion channels. This study also represents a new perspective for the treatment of envenomings in Roraima, since the Brazilian scorpion and arachnid antivenoms were not able to recognize R. crassicauda venom and its fractions (with exception of hyaluronidase). Our work provides useful insights for the first understanding of the painful sting and pro-inflammatory effects associated with R. crassicauda envenomings.

Scorpion toxins targeting Kv1.3 channels: insights into immunosuppression.

Scorpion venoms are natural sources of molecules that have, in addition to their toxic function, potential therapeutic applications. In this source the neurotoxins can be found especially those that act on potassium channels. Potassium channels are responsible for maintaining the membrane potential in the excitable cells, especially the voltage-dependent potassium channels (Kv), including Kv1.3 channels. These channels (Kv1.3) are expressed by various types of tissues and cells, being part of several physiological processes. However, the major studies of Kv1.3 are performed on T cells due its importance on autoimmune diseases. Scorpion toxins capable of acting on potassium channels (KTx), mainly on Kv1.3 channels, have gained a prominent role for their possible ability to control inflammatory autoimmune diseases. Some of these toxins have already left bench trials and are being evaluated in clinical trials, presenting great therapeutic potential. Thus, scorpion toxins are important natural molecules that should not be overlooked in the treatment of autoimmune and other diseases.

Scorpion toxins targeting Kv1 3 channels: insights into immunosuppression

Scorpion venoms are natural sources of molecules that have, in addition to their toxic function, potential therapeutic applications. In this source the neurotoxins can be found especially those that act on potassium channels. Potassium channels are responsible for maintaining the membrane potential in the excitable cells, especially the voltage-dependent potassium channels (Kv), including Kv1.3 channels. These channels (Kv1.3) are expressed by various types of tissues and cells, being part of several physiological processes. However, the major studies of Kv1.3 are performed on T cells due its importance on autoimmune diseases. Scorpion toxins capable of acting on potassium channels (KTx), mainly on Kv1.3 channels, have gained a prominent role for their possible ability to control inflammatory autoimmune diseases. Some of these toxins have already left bench trials and are being evaluated in clinical trials, presenting great therapeutic potential. Thus, scorpion toxins are important natural molecules that should not be overlooked in the treatment of autoimmune and other diseases.(AU)

Computational design of new protein kinase 2 inhibitors for the treatment of inflammatory diseases using QSAR, pharmacophore-structure-based virtual screening, and molecular dynamics.

Receptor-interacting protein kinase 2 (RIPK2) plays an essential role in autoimmune response and is suggested as a target for inflammatory diseases. A pharmacophore model was built from a dataset with ponatinib (template) and 18 RIPK2 inhibitors selected from BindingDB database. The pharmacophore model validation was performed by multiple linear regression (MLR). The statistical quality of the model was evaluated by the correlation coefficient (R), squared correlation coefficient (R2), explanatory variance (adjusted R2), standard error of estimate (SEE), and variance ratio (F). The best pharmacophore model has one aromatic group (LEU24 residue interaction) and two hydrogen bonding acceptor groups (MET98 and TYR97 residues interaction), having a score of 24.739 with 14 aligned inhibitors, which were used in virtual screening via ZincPharmer server and the ZINC database (selected in function of the RMSD value). We determined theoretical values of biological activity (logRA) by MLR, pharmacokinetic and toxicology properties, and made molecular docking studies comparing binding affinity (kcal/mol) results with the most active compound of the study (ponatinib) and WEHI-345. Nine compounds from the ZINC database show satisfactory results, yielding among those selected, the compound ZINC01540228, as the most promising RIPK2 inhibitor. After binding free energy calculations, the following molecular dynamics simulations showed that the receptor protein's backbone remained stable after the introduction of ligands.

The hygiene hypothesis at a glance: Early exposures, immune mechanism and novel therapies.

The hygiene hypothesis was proposed almost three decades ago. Nevertheless, its mechanism still remains with relevant controversies. Some studies defend that early exposures during childhood to microbes and parasites are key determinants to prevent allergies and autoimmune diseases; however, other studies demonstrated that these early exposures can even potentiate the clinical scenario of the diseases. Based on several studies covering the influences of microbiome, parasites, related theories and others, this review focuses on recent advances in the hygiene hypothesis field. In addition, the main immunological mechanisms underlying the hygiene hypothesis are also discussed. We also strongly encourage that researchers do not consider the hygiene hypothesis as a theory based strictly on hygiene habits, but a theory combining diverse influences, as illustrated in this review as the hygiene hypothesis net.

Step by step male to female transsexual surgery

ABSTRACT Introduction After the diagnosis of transsexualism is confirmed therapy commences with psychotherapeutic preparation for the conversion, and after conversion, long-term patient rehabilitation is maintained for at least two years. The indication for surgery is chronic discomfort caused by discord with the patient's natural gender, intense dislike of developing secondary sex characteristics and the onset of puberty. The surgical conversion of transsexuals is the main step in the complex care of these problematic patients (1). This surgery was first described by Benjamin H, using a flap of inverted penile skin (2) and is considered the gold standard since then. Male-to-female transsexual surgical techniques are well defined and give good cosmetic and functional results. Sex reassignment surgery promotes the improvement of psychological aspects and social relationships as shown in the World Health Organization Quality of Life Assessment applied in the patients submitted to this procedure (3). Techniques include the creation of a normal appearing female introitus, a vaginoplasty allowing sexual intercourse and the capability of clitoral orgasm (4). Various methods for neovaginoplasty have been described and can be classified into five categories, i.e. pedicled intestinal transplants, penile skin grafts, penile skin flaps, non-genital skin flaps and non-genital skin grafts (5). In our Hospital, we use penile and scrotal skin flaps. Until now, 174 procedures have been performed by our team using this technique with high rates of satisfaction (3). Patients and methods We present a step-by-step male to female transsexual surgery. Conclusion Surgical gender reassignment of male transsexuals resulted in replicas of female genitalia which enabled coitus with orgasm (1). With this video we show step by step that a surgery using penile skin flaps is able to be performed with good cosmetic results.

Step by step male to female transsexual surgery.

INTRODUCTION: After the diagnosis of transsexualism is confirmed therapy commences with psychotherapeutic preparation for the conversion, and after conversion, long-term patient rehabilitation is maintained for at least two years. The indication for surgery is chronic discomfort caused by discord with the patient's natural gender, intense dislike of developing secondary sex characteristics and the onset of puberty. The surgical conversion of transsexuals is the main step in the complex care of these problematic patients (1). This surgery was first described by Benjamin H, using a flap of inverted penile skin (2) and is considered the gold standard since then. Male-to-female transsexual surgical techniques are well defined and give good cosmetic and functional results. Sex reassignment surgery promotes the improvement of psychological aspects and social relationships as shown in the World Health Organization Quality of Life Assessment applied in the patients submitted to this procedure (3). Techniques include the creation of a normal appearing female introitus, a vaginoplasty allowing sexual intercourse and the capability of clitoral orgasm (4). Various methods for neovaginoplasty have been described and can be classified into five categories, i.e. pedicled intestinal transplants, penile skin grafts, penile skin flaps, non-genital skin flaps and non-genital skin grafts (5). In our Hospital, we use penile and scrotal skin flaps. Until now, 174 procedures have been performed by our team using this technique with high rates of satisfaction (3). PATIENTS AND METHODS: We present a step-by-step male to female transsexual surgery. CONCLUSION: Surgical gender reassignment of male transsexuals resulted in replicas of female genitalia which enabled coitus with orgasm (1). With this video we show step by step that a surgery using penile skin flaps is able to be performed with good cosmetic results.

Exploration of the Acetylcholinesterase Inhibitory Activity of Some Alkaloids from Amaryllidaceae Family by Molecular Docking In Silico.

Alzheimer's disease (AD) is a progressive condition, where dementia symptoms gradually worsen. Biochemically the disease is characterized by the presence of neuritic plaques, neurofibrillary tangles, in addition to cholinergic dysfunction in the central nervous system. The role of the cholinergic neurotransmission in AD is the basis of the widely accepted cholinergic hypothesis. Some of the most relevant therapies for the treatment of the disease are based on the acetylcholinesterase (AChE) inhibitor activity; however, these therapies are not effective to stop the disease progression, but only can temporarily slow down the worsening of dementia symptoms, and improve quality of life of patients and their caregivers. In recent years, plant alkaloids extracted from Amaryllidaceae family have received great attention due to the well-known anti cholinergic activity. In this context, the purpose of this study was to apply the docking molecular in sílico analysis aiming to examine the recombinant human AChE enzyme (rhAChE) inhibitory activity displayed by different alkaloids from Amaryllidaceae family. Overall, the present results support the idea that alkaloids reported in this research are capable of interacting with rhAChE-binding sites.