Photodynamic therapy and adapalene in dermatology: synergistic effects in immortal human keratinocytes

We compared the effects of methyl levulinate (MAL)/photodynamic therapy (PDT) and adapalene, evaluated singly, versus combination therapy on HaCaT keratinocytes. Our aim was to determine whether the additive/synergistic outcomes of combination treatment were such that doses of each component could be reduced without affecting treatment efficacy. The analysis of data from specific PDT/adapalene combinations results indicating effects ranging from additive to clearly synergistic. We first evaluated the effects on cell viability, cell cycle and protein expression profiles of each individual treatment, then we tried to understand the reasons and the mechanisms whereby cells under combined treatment move more efficiently to death. Although we observed therapeutic strengthening by increasing either drug doses or light fluences, reinforcement was particularly marked in combinations in which PDT was predominant. Thus, if PDT is appropriately tuned, the dose of the drug can be reduced without compromising the therapeutic response. As both photodynamic therapy and adapalene have been and are therapeutic approaches to treat different dermatological pathologies such as acne, actinic keratosis etc., our data suggest that the adapalene-PDT combination may have important spin-off in clinical dermatology as a strategy to tackle this nasty condition

The computation of reproduction numbers for the environment-host-environmen cholera transmission dynamics

This study presents a new model for the environment-host-environment transmission dynamics of V. cholerae in a community with an interconnected aquatic pond–river water network. For the case when the human host is the sole target of anti-cholera control and the volume of water in the pond is maximum, the disease-free equilibrium of the model is shown to be globally asymptotically stable whenever a certain epidemiological threshold, known as the basic reproduction number, is less than unity. The epidemiological implication of this result is that cholera can be eliminated from the community if the control strategies implemented can bring (and maintain) the basic reproduction number to a value less than unity. Four scenarios, that represent different interpretations of the role of the V. cholerea pathogen within the environment, were studied. The corresponding basic reproduction numbers were shown to exhibit the same threshold property with respect to the value unity (i.e., if one is less (equal, greater) than unity, then the three others are also less (equal, greater) than unity. Further, it was shown that for the case where anti-cholera control is focused on the human host population, the associated type reproduction number of the model (corresponding to each of the four transmission scenarios considered) is unique. The implication of this result is that the estimate of the effort needed for disease elimination (i.e., the required herd immunity threshold) is unique, regardless of which of the four transmission scenarios is considered. However, when any of the other two bacterial population types in the aquatic environment (i.e., bacterial in the pond or river) is the focus of the control efforts, this study shows that the associated type reproduction number is not unique. Extensive numerical simulations of the model, using a realistic set of parameters from the published literature, show that the community-wide implementation of a strategy that focus on improved water quality, sanitation, and hygiene (known as WASH-only strategy), using the current estimated coverage of 50% and efficacy of 60%, is unable to lead to the elimination of the disease. Such elimination is attainable if the coverage and efficacy are increased (e.g., to 80% and 90%, respectively). Further, elimination can be achieved using a strategy that focuses on oral rehydration therapy and the use of antibiotics to treat the infected humans (i.e., treatment-only strategy) for moderate effectiveness and coverage levels. The combined hybrid WASH-treatment strategy provides far better population-level impact vis a vis disease elimination. This study ranks the three interventions in the following order of population-level effectiveness: combined WASH-treatment, followed by treatment-only and then WASH-only strategy.Gruppo Nazionale per la Fisica Matematica (GNFM), the Istituto Nazionale di Alta Matematica Francesco Severi (INdAM) of Italy, the Simons Foundation and the National Science Foundation.https://www.worldscientific.com/worldscinet/jbs2021-02-13hj2020Mathematics and Applied Mathematic

Approximate Asymptotic Symmetries

We modify the procedure of determining approximate one parameter group of transformations by introducing an asymptotic development which makes possible the matching between dissipative or dispersive effects and non-linearity. Once that the generators of the approximate group are determined approximate asymptotic invariant solutions can be determine

A mathematical model of vertically transmitted vector diseases

A mathematical model of vector-borne infectious diseases is presented, which takes into account the local interactions between reservoirs and vectors, as well as the transmission from vectors to dilution hosts. In the model, vectors possess the ability to keep the virus within their own population through vertical transmission. The existence and the stability of disease free and endemic equilibria, together with the existence of backward bifurcation, are discussed