Bacterial Toxin–Antitoxin Systems: More Than Selfish Entities?

Bacterial toxin–antitoxin (TA) systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence, they may contribute to the maintenance of plasmids or genomic islands, such as super-integrons, by post-segregational killing of the cell that loses these genes and so suffers the stable toxin's destructive effect. The function of the chromosomally encoded TA systems is less clear and still open to debate. This Review discusses current hypotheses regarding the biological roles of these evolutionarily successful small operons. We consider the various selective forces that could drive the maintenance of TA systems in bacterial genomes

Quantitative clinical pharmacology practice for optimal use of antibiotics during the neonatal period

Introduction: For safe and effective neonatal antibiotic therapy, knowledge of the pharmacokinetic parameters of antibacterial agents in neonates is a prerequisite. Fast maturational changes during the neonatal period influence pharmacokinetic and pharmacodynamic parameters and their variability. Consequently, the need for applying quantitative clinical pharmacology and determining optimal drug dosing regimens in neonates has become increasingly recognized. Areas covered: Modern quantitative approaches, such as pharmacometrics, are increasingly utilized to characterize, understand and predict the pharmacokinetics of a drug and its effect, and to quantify the variability in the neonatal population. Individual factors, called covariates in modeling, are integrated in such approaches to explain inter-individual pharmacokinetic variability. Pharmacometrics has been shown to be a relevant tool to evaluate, optimize and individualize drug dosing regimens. Expert opinion: Challenges for optimal use of antibiotics in neonates can largely be overcome with quantitative clinical pharmacology practice. Clinicians should be aware that there is a next step to support the clinical decision-making based on clinical characteristics and therapeutic drug monitoring, through Bayesian-based modeling and simulation methods. Pharmacometric modeling and simulation approaches permit us to characterize population average, inter-subject and intra-subject variability of pharmacokinetic parameters such as clearance and volume of distribution, and to identify and quantify key factors that influence the pharmacokinetic behavior of antibiotics during the neonatal period

Teor de óleo e de cafeína em variedades de café Oil and caffeine content in the coffee bean

Determinou-se a porcentagem de óleo e de cafeína em sementes de diversas variedades de Coffee arabica. As sementes provieram de frutos despolpados, secos em terreiro sem despolpar, ou secos na própria planta. O tratamento des frutos influiu sôbre o teor de óleo, sendo também significativa a diferença entre as variedades. Os dados confirmam resultados anteriores de que a variedade mucronata é rica e a, variedade laurina, pobre, em óleo. No que concerne ao teor de cafeína, o tratamento dos frutos não mostrou influência, mas pronunciada diferença se constatou entre as variedades. Sete das variedades se mostraram mais pobres do que o café 'Sumatra', tomado comg padrão. A variedade laurina destacou-se das demais pelo baixo teor dêsse alcalóide com, aproximadamente, a metade do nível encontrado nas demais variedades analisadas, o que a torna valiosa para um piano de melhoramento visando a redução do nível de cafeína nas sementes.<br>Oil and caffeine contents were determined for seed samples obtained from cherries of sixteen varieties of Coffea arabica which were submitted to three types of treatments pulped, non pulped and left to dry with pericarp in the sun, or naturally dried on the tree. Cherry processing seems not to have influence on the oil content in the seeds (table I), but significant differences were noted among the varieties with respect to this characteristic. Mucronata revealed to have high oil content while the laurina is a low oil producing variety. Coffee cherries left to dry on the trees gave lower caffeine content. Seven of the sixteen varieties presented a lower caffeine content than the standard 'Sumatra'. The laurinis variety had an exceptional lower caffeine content of about half the amount found in the control. Laurina characteristics are controlled by a recessive allele lr with strong pleiotropic effects. It is not yet known how the laurina allele affects the chemical reactions which lead to a so low caffeine content in the coffee bean. The value of the lr allele was stressed in reducing the caffeine content in the coffee selected cultivars

Pharmacometrics-based decision tools facilitate mHealth implementation.

The healthcare system is experiencing a paradigm shift in delivering its services, evolving from a reactive 'one size-fits-all' structure to a patient-centric model focusing on individualized medicine. This change is driven by scientific progress, including quantitative evaluation and optimization of treatment strategies through pharmacometric approaches, harnessing the power of the digital revolution. Areas covered: This review describes four main steps to apply pharmacometrics-based decision support tools, consisting of validated scientific components, available technical options, consideration of regulatory aspects, and achievement of efficient commercialization. Examples of pharmacometrics-based decision tools that support monitoring of patients and individualization of treatment strategies in neonates, children and adults are presented. Expert commentary: We envision that user-friendly decision support tools will facilitate implementation of mobile health approaches (mHealth) realizing benefits to paediatric and adult patients and their caregivers

A eliminação da substância péctica do café despolpado é causada por microrganismos The elimination of the pectic substances which involves the seeds of pulped coffee is due to microorganisms

Em trabalhos recentemente publicados. Pereira (9, 10) conclui que os frutos de café possuem enzimas capazes de eliminar a substância péctica que envolve as sementes, quando após o despolpomento são eles colocados em água de cal contendo 0,4% de cloreto de sódio. No presente trabalho mostra-se que aquela substância péctica não é eliminada pelo tratamento descrito, mas apenas torna-se endurecida pela ação do cálcio. Quando sementes tratadas da maneira indicada foram lavadas e colocadas em água pura ou levemente acidulada, a substância péctica se reintumesceu e as sementes tornaram-se novamente lisas ao tato e envolvidas pela camada translúcida de substância péctica. Esta conclusão confirma os trabalhos anteriormente publicados (3, 4), que mostraram ser a eliminação da substância péctica, que envolve as sementes de café despolpado, devida a mícrorganismos.<br>In papers recently published, Pereira Jr. (9, 10) claimed that coffee fruits have enzimes capable of breaking down the insoluble pectic substance which involves their seeds. This conclusion was drawn from an experiment where freshly pulped coffee fruits were placed in a calcium hydroxide solution containing 0.4% of NaCl as an enzime activator. After this treatment the seeds which were very slimy became apparently clean and could be handled easily. In this paper it is shown that the pectic substance is not eliminated by such a treatment but that it merely becomes herdened by the action of the calcium hydroxide. When seeds so treated were washed and left in water the pectic substance involving the seeds became turgid again giving the seeds the same slimy feeling to the touch that was noticeable prior to the treatment. This process is enhanced by the use of acidulated water after the washing. These results support the conclusions of previous papers (3, 4) showing that the elimination of the pectic substances in pulped coffee berries is due to microorganisms

Unveiling the Structure of the Marrakech Medina: A shape grammar and an interpreter for generating urban form

This paper describes research carried out to develop a parametric urban shape grammar for the Zaouiat Lakhdar quarter of the Medina of Marrakech in Morocco. The goal is to create the basis for a system that could capture some features of the existing urban fabric and apply them in contemporary urban planning and architectural design. The methodology used is described, from the initial historical analysis and fieldwork to the identification of three subgrammars necessary to encode the complexity of the urban preexistences: the urban grammar, the negotiation grammar, and the housing grammar. Top-down and bottom-up approaches to grammar design are analyzed and compared. The bottom-up urban grammar developed is then described, and a hand derivation of the existing urban fabric is proposed. Visual, symbolic, and tagged computer implementations of shape grammars are briefly discussed and a novel design generated by the tagged interpreter is presented

Identification of Most Aggressive Carcinoma Among Patients Diagnosed With Prostate Cancer Using Mathematical Modeling of Prostate-Specific Antigen Increases

International audienceBACKGROUND: Tools for differentiating aggressive and indolent prostate carcinoma (PCa) are needed. Mathematical modeling is a promising approach for longitudinal analysis of tumor marker kinetics. PATIENTS AND METHODS: The prostate-specific antigen (PSA) increases from patients with PCa and those with benign prostatic hyperplasia (BPH) were retrospectively analyzed using a mathematical model. Using the NONMEM program, individual PSA kinetics were fit to the following equation: [d(PSA)/dt = (PROD.K x exp [RHO1 x t]) x (1 - BPH) + PROD.NK x exp (RHO2 x t) - KELIM x (PSA)], where RHO1 is the PSA production increase rate by PCa cells (PROD.K), RHO2 is the PSA production increase rate by non-PCa cells (PROD.NK), and KELIM is the PSA elimination rate. The comparative value of the modeled kinetic parameters, estimated for each patient, for predicting the D'Amico score and relapse-free survival (RFS) were tested using logistic regression analysis and multivariate survival tests. RESULTS: The PSA kinetics from 62 patients with BPH and 149 patients with PCa before radical prostatectomy were successfully modeled. We identified statistically significant relationships between the PSA growth rate related to cancer cells (RHO1) and the probability of D'Amico high-risk group (less than the median RHO1 vs. at the median or greater: odds ratio, 2.15; 95% confidence interval [CI], 1.00-4.77; P = .05). RHO1 was also a significant prognostic factor for RFS on univariate analysis and against other reported prognostic factors using multivariate Cox tests. Three independent prognostic factors of RFS were found: RHO1 (hazard ratio [HR], 2.71; 95% CI, 1.25-5.84; P = .01), Gleason score (HR, 8.54; 95% CI, 4.19-17.40; P \textless .01), and positive surgical margins (HR, 2.04; 95% CI, 1.05-3.97; P = .03). CONCLUSION: Using a few PSA time points analyzed with a mathematical model (easily manageable in routine practice), it could be possible to determine before surgery whether a patient has presented with aggressive PC