Antigen receptor therapy in bone metastasis via optimal control for different human life stages.

In this work we propose a bone metastasis model using power law growth functions in order to describe the biochemical interactions between bone cells and cancer cells. Experimental studies indicate that bone remodeling cycles are different for human life stages: childhood, young adulthood, and adulthood. In order to include such differences in our study, we estimate the model parameter values for each human life stage via bifurcation analysis. Results reveal an intrinsic relationship between the active period of remodeling cycles and the proliferation of cancer cells. Subsequently, using optimal control theory we analyze a possible antigen receptor therapy as a new treatment for bone metastasis. Theoretical results such as existence of optimal solutions are proved. Numerical simulations for late stages of bone metastasis are presented and a discussion of our results is carried out.

Mercury Levels in Feathers of Penguins from the Antarctic Peninsula Area: Geographical and Inter-Specific Differences.

Polar regions, symbols of wilderness, have been identified as potential sinks of mercury coming from natural and anthropogenic sources at lower latitudes. Changes in ice coverage currently occurring in some areas such as the Antarctic Peninsula could enhance these phenomena and their impacts on local biota. As long-lived species at the top of food chains, seabirds are particularly sensitive to this highly toxic metal with the capacity to be biomagnified. Specifically, their feathers can be useful for Hg monitoring since they mainly accumulate its most toxic and persistent form, methyl-Hg. To that end, feathers of gentoo (Pygoscelis papua), chinstrap (P. antarcticus), and Adélie penguins (P. adeliae) (n = 108) were collected by passive sampling in seven different locations throughout the Antarctic Peninsula area and analyzed by ICP-MS after microwave-digestion. More than 93% of the samples showed detectable Hg levels (range: 6.3-12,529.8 ng g-1 dry weight), and the highest ones were found in the feathers of chinstrap penguins from King George Island. Hg bioconcentration and biomagnification seem to be occurring in the Antarctic food web, giving rise to high but non-toxic Hg levels in penguins, similar to those previously found in Arctic seabirds.

Strange attractors in discrete slow power-law models of bone remodeling.

Recently, a family of nonlinear mathematical discrete systems to describe biological interactions was considered. Such interactions are modeled by power-law functions where the exponents involve regulation processes. Considering exponent values giving rise to hyperbolic equilibria, we show that the systems exhibit irregular behavior characterized by strange attractors. The systems are numerically analyzed for different parameter values. Depending on the initial conditions, the orbits of each system either diverge to infinity or approach a periodic orbit or a strange attractor. Such dynamical behavior is identified by their Lyapunov exponents and local dimension. Finally, an application to the biochemical process of bone remodeling is presented. The existence of deterministic chaos in this process reveals a possible explanation of reproducibility failure and variation of effects in clinical experiments.

Modeling Public Health Campaigns for Sexually Transmitted Infections via Optimal and Feedback Control.

Control of sexually transmitted infections (STIs) poses important challenges to public health authorities. Obstacles for STIs' control include low priority in public health programs and disease transmission mechanisms. This work uses a compartmental pair model to explore different public health strategies on the evolution of STIs. Optimal control and feedback control are used to model realistic strategies for reducing the prevalence of these infections. Feedback control is proposed to model the reaction of public health authorities relative to an alert level. Optimal control is used to model the optimization of available resources for implementing strategies. Numerical simulations are performed using trichomoniasis, gonorrhea, chlamydia and human papillomavirus (HPV) as study cases. HPV is non-curable, and it is analyzed only under transmission control such as condom promotion campaigns. Trichomoniasis, gonorrhea and chlamydia are curable STIs that are modeled here additionally under treatment control. Increased cost-effectiveness ratio is employed as a criterion to measure control strategies performance. The features and drawbacks of control strategies under the pair formation process are discussed.

Bone metastasis treatment modeling via optimal control.

Metastatic disease is a lethal stage of cancer progression. It is characterized by the spread of aberrant cells from a primary tumor to distant tissues like the bone. Several treatments are used to deal with bone metastases formation, but they are palliative since the disease is considered incurable. Computational and mathematical models are used to understand the underlying mechanisms of how bone metastasis evolves. In this way, new therapies aiming to reduce or eliminate the metastatic burden in the bone tissue may be proposed. We present an optimal control approach to analyze some common treatments for bone metastasis. In particular, we focus on denosumab treatment, an anti-resorptive therapy, and radiotherapy treatment which has a cell killing action. We base our work in a variant of an existing model introduced by Komarova. The new model incorporates a logistic equation in order to describe the bone metastasis evolution. We provide proofs of existence and uniqueness of solutions to the corresponding optimal control problems for each treatment. Moreover, we present some numerical simulations to analyze the effectiveness of both treatments when different interactions between cancer and bone cells occur. A discussion of the obtained results is provided.

MODE OF ATTACHMENT AND PATHOLOGY CAUSED BY PARORCHITES ZEDERI IN THREE SPECIES OF PENGUINS: PYGOSCELIS PAPUA, PYGOSCELIS ADELIAE, AND PYGOSCELIS ANTARCTICA IN ANTARCTICA.

We identified and compared gross and microscopic lesions associated with the cestode, Parorchites zederi, in the digestive tracts of three species of penguins (Spheniscidae): the Chinstrap ( Pygoscelis antarctica ), Gentoo ( Pygoscelis papua ), and Adélie penguins ( Pygoscelis adeliae ). The gastrointestinal tracts of 79 recently dead individuals (71 chicks and eight adults) were collected in locations throughout the Antarctic Peninsula during summer field trips in 2006-09. Parorchites zederi was found in the small intestine of 37 animals (47%), and 23 (62%) of these had parasite-associated lesions. The cestodes were either free in the intestinal lumen, clustered within mucosal ulcers, or deeply embedded in the intestinal wall. Histopathologic changes were most severe in adult Gentoo Penguins and included transmural fibrogranulomatous enteritis, hemorrhage, and edema. This report of pathology associated with P. zederi in the digestive tracts of penguins can serve as reference to monitor health in Antarctic birds associated with environmental changes.

Monitoring trace elements in Antarctic penguin chicks from South Shetland Islands, Antarctica.

The concentration of human activities in the near-shore ecosystems from the northern Antarctic Peninsula area can cause an increasing bioavailability of pollutants for the vulnerable Antarctic biota. Penguin chicks can reflect this potential impact in the rookeries during the breeding season. They also can reflect biomagnification phenomena since they are on the top of the Antarctic food chain. The concentrations of Al, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Cd and Pb were measured by ICP-MS in samples of liver, kidney, muscle, bone, feather and stomach content of gentoo, chinstrap and Adélie penguin chicks (n=15 individuals) collected opportunistically in the Islands of King George and Deception (South Shetland Islands, Antarctica). The detected levels of some trace elements were not as low as it could be expected in the isolated Antarctic region. Penguin chicks can be useful indicators of trace elements abundance in the study areas. CAPSULE: Carcasses of Antarctic penguin chicks were used to evaluate the bioavailability of trace elements in the Islands of King George and Deception.

Gastrointestinal helminths of Gentoo penguins (Pygoscelis papua) from Stranger Point, 25 de Mayo/King George Island, Antarctica.

The aim of this work is to contribute to the knowledge of gastrointestinal parasites of the Gentoo penguin (Pygoscelis papua) from 25 de Mayo/King George Island (South Shetlands, Antarctica). Gastrointestinal tracts of 37 fresh dead individuals (21 chicks, 10 juveniles, and 6 adults) were collected from December 2006 to February 2012 and examined for macroparasites. Four adult parasite species were found: one Cestoda species (Parorchites zederi), two Nematoda species (Stegophorus macronectes and Tetrameres wetzeli), and one Acanthocephalan (Corynosoma shackletoni). Two species of immature acanthocephalans, Corynosoma hamanni and Corynosoma bullosum, were found in a single host. This is the first record of Tetrameres wetzeli in Gentoo penguins. The low parasite richness observed could be related to the stenophagic and pelagic diet of this host species which feeds almost exclusively on krill.

Distribution of metals and trace elements in adult and juvenile penguins from the Antarctic Peninsula area.

The presence of metals in the Antarctic environment is principally a natural phenomenon caused by geochemical characteristics of the region, although some anthropogenic activities can increase these natural levels. Antarctic penguins present several of the characteristics of useful sentinels of pollution in Antarctica such as they are long-lived species situated at the top of food web. The concentrations of Al, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Cd, and Pb were determined by inductively coupled plasma-mass spectrometry in samples of liver, kidney, muscle, bone, feather, and stomach contents of gentoo, chinstrap, and Adélie penguin (12 adults, five juveniles) from carcasses of naturally dead individuals collected opportunistically in the Antarctic Peninsula area. The obtained results showed that accumulation and magnification of several elements can be occurring, so that Cd and Se reached levels potentially toxic in some specimens. The presence of human activities seems to be increasing the presence of toxic metals such as Mn, Cr, Ni, or Pb in penguins.

Concentration of trace elements in feathers of three Antarctic penguins: geographical and interspecific differences.

Antarctica is often considered as one of the last pristine regions, but it could be affected by pollution at global and local scale. Concentrations of Al, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Cd and Pb were determinated by ICP-MS in feathers (n = 207 individuals) of gentoo, chinstrap and Adélie penguin collected in 8 locations throughout the Antarctic Peninsula (2006-2007). The highest levels of several elements were found in samples from King George Island (8.08, 20.29 and 1.76 µg g(-1) dw for Cr, Cu and Pb, respectively) and Deception Island (203.13, 3.26 and 164.26 µg g(-1) dw for Al, Mn and Fe, respectively), where probably human activities and large-scale transport of pollutants contribute to increase metal levels. Concentrations of Cr, Mn, Cu, Se or Pb, which are similar to others found in different regions of the world, show that some areas in Antarctica are not utterly pristine.

Accumulation and tissue distribution of heavy metals and essential elements in loggerhead turtles (Caretta caretta) from Spanish Mediterranean coastline of Murcia.

Sea turtles are of increasing interest as potential bioindicators of the heavy metal pollution in marine ecosystems. In the present work, concentrations of heavy metals and essential elements (As, Cd, Hg, Pb, Se, Zn) in different organs and tissues (liver, kidney, muscle, bone, blood, central nervous system and skin) of loggerhead sea turtles (Caretta caretta) were determined from stranded animals found along the Spanish Mediterranean coastlines of Murcia. Relatively high average levels of As (skin: 52.13 microg g(-1) dry weight; muscle: 40.95 microg g(-1) dry weight), and especially high individual levels of Zn in muscle tissue (1002.4 microg g(-1) dry weight) were detected. Furthermore, a significant degree of organotrophism of Cd was observed in kidney tissue. The concentrations detected, the distribution among the tissues and the differences observed between juvenile and adult specimens are generally compatible with chronic exposure to the elements studied, whilst levels produced by acute exposure were ruled out.