Effect of tumor shape,size, and tissue transport properties on drug delivery to solid tumors

Background

The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, drug extravasation from microvessels or to lymphatic vessels. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to investigate the effect of tumor shape and size on drug delivery to solid tumor.

Methods

The advanced mathematical model used in our previous work is further developed by adding solute transport equation to the governing equations. After applying appropriate boundary and initial conditions on tumor and surrounding tissue geometry, the element-based finite volume method is used for solving governing equations of drug delivery in solid tumor. Also, the effects of size and shape of tumor and some of tissue transport parameters such as effective pressure and hydraulic conductivity on interstitial fluid flow and drug delivery are investigated.

Results

Sensitivity analysis shows that drug delivery in prolate shape is significantly better than other tumor shapes. Considering size effect, increasing tumor size decreases drug concentration in interstitial fluid. This study shows that dependency of drug concentration in interstitial fluid to osmotic and intravascular pressure is negligible.

Conclusions

This study shows that among diffusion and convection mechanisms of drug transport, diffusion is dominant in most different tumor shapes and sizes. In tumors in which the convection has considerable effect, the drug concentration is larger than that of other tumors at the same time post injection.

     

Reward Maximization Justifies the Transition from Sensory Selection at Childhood to Sensory Integration at Adulthood

In a multisensory task, human adults integrate information from different sensory modalities -behaviorally in an optimal Bayesian fashion- while children mostly rely on a single sensor modality for decision making. The reason behind this change of behavior over age and the process behind learning the required statistics for optimal integration are still unclear and have not been justified by the conventional Bayesian modeling. We propose an interactive multisensory learning framework without making any prior assumptions about the sensory models. In this framework, learning in every modality and in their joint space is done in parallel using a single-step reinforcement learning method. A simple statistical test on confidence intervals on the mean of reward distributions is used to select the most informative source of information among the individual modalities and the joint space. Analyses of the method and the simulation results on a multimodal localization task show that the learning system autonomously starts with sensory selection and gradually switches to sensory integration. This is because, relying more on modalities -i.e. selection- at early learning steps (childhood) is more rewarding than favoring decisions learned in the joint space since, smaller state-space in modalities results in faster learning in every individual modality. In contrast, after gaining sufficient experiences (adulthood), the quality of learning in the joint space matures while learning in modalities suffers from insufficient accuracy due to perceptual aliasing. It results in tighter confidence interval for the joint space and consequently causes a smooth shift from selection to integration. It suggests that sensory selection and integration are emergent behavior and both are outputs of a single reward maximization process; i.e. the transition is not a preprogrammed phenomenon.     

Polycyclic Aromatic Hydrocarbons in Coastal Sediment of Klang Strait,Malaysia: Distribution Pattern,Risk Assessment and Sources

Concentration, source, and ecological risk of polycyclic aromatic hydrocarbons (PAHs) were investigated in 22 stations from surface sediments in the areas of anthropogenic pollution in the Klang Strait (Malaysia). The total PAH level in the Klang Strait sediment was 994.02±918.1 µg/kg dw. The highest concentration was observed in stations near the coastline and mouth of the Klang River. These locations were dominated by high molecular weight PAHs. The results showed both pyrogenic and petrogenic sources are main sources of PAHs. Further analyses indicated that PAHs primarily originated from pyrogenic sources (coal combustion and vehicular emissions), with significant contribution from petroleum inputs. Regarding ecological risk estimation, only station 13 was moderately polluted, the rest of the stations suffered rare or slight adverse biological effects with PAH exposure in surface sediment, suggesting that PAHs are not considered as contaminants of concern in the Klang Strait.     

Scaling-Up Access to Family Planning May Improve Linear Growth and Child Development in Low and Middle Income Countries

Background

A large literature has indicated a robust association between birth spacing and child survival, but evidence on the association of birth timing with physical growth in low and middle income countries (LMICs) remains limited.

Methods and Results

Data from 153 cross-sectional Demographic and Health Surveys (DHS) across 61 LMICs conducted between 1990 and 2011 were combined to assess the association of birth timing with child stunting (height-for-age z-score <−2). A total of 623,789 children of birth order 1–5 contributed to the maternal age analysis, while the birth spacing dataset consisted of 584,226 children of birth order 2 and higher. Compared to 27–34 year old mothers, maternal age under 18 years was associated with a relative stunting risk of 1.35 (95% CI: 1.29–1.40) for firstborn children, whereas the relative risk was 1.24 (95% CI: 1.19–1.29) for mothers aged 18–19 years. The association of young maternal age with stunting was significantly greater for urban residents and those in the top 50% of household wealth. Birth intervals less than 12 months and 12–23 months had relative risks for stunting of 1.09 (95% CI: 1.06–1.12) and 1.06 (95% CI: 1.05–1.06) as compared to a 24–35 month inter-pregnancy interval, respectively. The strength of both teenage pregnancy and short birth interval associations showed substantial variation across WHO region. We estimate that 8.6% (6.9–10.3%) of stunted cases in the South Asian DHS sample would have been averted by jointly eliminating teen pregnancies and birth intervals less than 24 months, while only 3.6% (1.5–5.7%) of stunting cases would have prevented in the Middle East and North Africa sample.

Conclusions

Postponing the age of first birth and increasing inter-pregnancy intervals has the potential to significantly reduce the prevalence of stunting and improve child development in LMICs.     

Application of mesenchymal stem cells in regenerative medicine: A new approach in modern medical science

Mesenchymal Stem Cells (MSCs) are non-hematopoietic and multipotent stem cells, which have been considered in regenerative medicine. These cells are easily separated from different sources, such as bone marrow (BM), umbilical cord (UC), adipose tissue (AT), and etc. MSCs have the differentiation capability into chondrocytes, osteocytes, and adipocytes; This differentiation potential along with the paracrine properties have made them a key choice for tissue repair. MSCs also have various advantages over other stem cells, which is why they have been extensively studied in recent years. The effectiveness of MSCs-based therapies depend on several factors, including differentiation status at the time of use, concentration per injection, delivery method, the used vehicle, and the nature and extent of the damage. Although, MSCs have emerged promising sources for regenerative medicine, there are potential risks regarding their safety in their clinical use, including tumorigenesis, lack of availability, aging, and sensitivity to toxic environments. In this study, we aimed to discuss how MSCs may be useful in treating defects and diseases. To this aim, we will review recent advances of MSCs action mechanisms in regenerative medicine, as well as the most recent clinical trials. We will also have a brief overview of MSCs resources, differences between their sources, culture conditions, extraction methods, and clinical application of MSCs in various fields of regenerative medicine.     

Susceptibility to photoinhibition in seedlings of six tropical fruit tree species native to Malaysia following transplantation to a degraded land

To investigate the adaptive capacity to a strong light environment when planted on degraded land, we examined photosynthetic properties in relation to photoinhibition for the sun-leaves of six tropical fruit tree species native to Malaysia before and after transplanting. The six species were: Bouea macrophylla (Bm), Callerya atropurpurea (Ca), Canarium pilosum (Cp), Cynometra cauliflora (Cc), Morinda citrifolia (Mc) and Syzygium sp. (Ssp), which produce edible fruit for endemic animals and birds, and are candidates for corridor plantations. Based on the measurements performed before transplanting, the degree of chronic photoinhibition indicated by the decrease in pre-dawn F _v/F _m was well associated with an accumulation of excessive excitation energy in PSII indicated by a decrease in photochemical quenching (qP). Among the species, Ca and Mc showed lower degrees of photoinhibition with higher qP. Higher electron transport rates (ETR) were observed with higher qP whereas there was no significant relationship between regulatory thermal dissipation (indicated by ) and qP. Energy dissipation via electron transport was suggested to be important in keeping qP high and preventing photoinhibition when compared among species. Cc and Bm showed lower ETR and higher susceptibility to photoinhibition before and after transplanting. New Cp and Mc leaves developed after transplanting showed increased area-based leaf nitrogen content (N _area) and stomatal conductance (gs) compared with those before transplanting resulting in higher light-saturated net photosynthetic rates (A _max) and ETR, and contributing to mitigate photoinhibition. In contrast to these species, Ca achieved high A _max with a water conservative manner (indicated by its relatively lower gs), where the higher carboxylation efficiency accompanied with the higher N _area allowed them to maintain relatively high A _max and ETR at lower intercellular CO₂ concentration.