Correction to: Q‑S laser micro‑drilling and multipass full‑beam Q‑S laser for tattoo removal — a case series

Lasers in Medical Science -     

Seroepidemiology of hepatitis E in patients on haemodialysis in Croatia

International Urology and Nephrology - Data on the seroprevalence of hepatitis E virus (HEV) in heamodialysis (HD) patients are conflicting, ranging from 0 to 44%. The aim of this study was to...     

Mechanistic Understanding of Brain Drug Disposition to Optimize the Selection of Potential Neurotherapeutics in Drug Discovery

Purpose

The current project was undertaken with the aim to propose and test an in-depth integrative analysis of neuropharmacokinetic (neuroPK) properties of new chemical entities (NCEs), thereby optimizing the routine of evaluation and selection of novel neurotherapeutics.

Methods

Forty compounds covering a wide range of physicochemical properties and various CNS targets were investigated. The combinatory mapping approach was used for the assessment of the extent of blood-brain and cellular barriers transport via estimation of unbound-compound brain (K_p,uu,brain) and cell (K_p,uu,cell) partitioning coefficients. Intra-brain distribution was evaluated using the brain slice method. Intra- and sub-cellular distribution was estimated via calculation of unbound-drug cytosolic and lysosomal partitioning coefficients.

Results

Assessment of K_p,uu,brain revealed extensive variability in the brain penetration properties across compounds, with a prevalence of compounds actively effluxed at the blood-brain barrier. K_p,uu,cell was valuable for identification of compounds with a tendency to accumulate intracellularly. Prediction of cytosolic and lysosomal partitioning provided insight into the subcellular accumulation. Integration of the neuroPK parameters with pharmacodynamic readouts demonstrated the value of the proposed approach in the evaluation of target engagement and NCE selection.

Conclusions

With the rather easily-performed combinatory mapping approach, it was possible to provide quantitative information supporting the decision making in the drug discovery setting.     

The Role of Public Health Advocacy in Achieving an Outright Ban on Commercial Tanning Beds in Australia

Although many countries still face opposition to the legislation of artificial tanning beds, all Australian states and territories have announced a total ban on commercial tanning beds. A combination of epidemiological and policy-centered research, powerful personal stories, and the active advocacy of prominent academics, cancer organizations, and grassroots community campaigners contributed to the decisions to first legislate standards and then ban all commercial tanning beds. We have illustrated that incremental change can be an effective pathway to securing substantial public health reforms.The Evidence Linking Artificial tanning beds to melanoma risk is now unequivocal. In 2006, the International Agency for Research in Cancer released a systematic review that proved to be significant in raising awareness of the harmful effects of tanning bed use.1 A more recent update of this systematic review of the literature concluded that the increased risk of melanoma associated with early tanning bed use was 59% for people whose first exposure to artificial ultraviolet radiation in a suntanning unit occurred before aged 35 years and that risk increased with the number of tanning bed sessions per year.2,3With the evidence of increased risk of melanoma and other skin cancers growing, legislative controls to ban access to commercial tanning beds for those younger than 18 years have been implemented in nearly 20 countries,4 almost all since 2006, indicating the influence of the International Agency for Research in Cancer report along with local public health advocacy efforts. However, tanning bed control advocates in many countries still face opposition. For example, in the United States, although there are more than 30 states that have some controls related to tanning bed use, only California, Vermont, Oregon, Texas, Nevada, and Illinois have introduced statewide bans for those younger than 18 years.     

1-Methyl-1,2,3,4-tetrahydroisoquinoline,an Endogenous Neuroprotectant and MAO Inhibitor with Antidepressant-Like Properties in the Rat

Oxidative stress is a major contributing factor in a range of brain pathologies and in the etiology of depression. 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous substance which is present in the mammalian brain and exhibits neuroprotective, and monoamine oxidase (MAO)-inhibiting properties. In the present study, in order to investigate the potential role of 1MeTIQ as an antidepressant, we tested antidepressant-like effects of 1MeTIQ in comparison with desipramine (a classic antidepressant) in the forced swimming test (FST), and using HPLC methodology, we measured the concentrations of monoamines (dopamine, noradrenaline, serotonin) and the rate of their metabolism. 1MeTIQ given alone as well as in combination with desipramine produced an antidepressant-like effect and decreased the immobility time in the FST. Neurochemical data have shown that 1MeTIQ like desipramine, activated the noradrenergic system. However, the mechanism of action of 1MeTIQ is broader than the actions of desipramine, and 1MeTIQ inhibits the MAO-dependent oxidation of dopamine and serotonin in all investigated structures. We can conclude that 1MeTIQ exhibits antidepressant-like activity in the FST in the rat. The mechanism of its antidepressant action differs from desipramine and seems to be mostly associated with the inhibition of the catabolism of monoamines and their increased concentrations in the brain. 1MeTIQ seems to be very beneficial from the clinical point of view as a reversible MAO inhibitor with a significant antidepressant effects.     

Influence of Nutrition and Lifestyle on Bone Mineral Density in Children From Adoptive and Biological Families

Background

The precise contributions of hereditary and environmental factors to bone density are not known. We compared lifestyle predictors of bone density among adopted and biological children.

Methods

The study comprised 18 adopted children (mean [SD] age, 14.0 [4.1] years) with their non-biological parents and 17 children with their biological parents. Bone mineral density (BMD; g/cm²) was measured at the lumbar spine, total femur, and distal radius. Nutritional intake was assessed by food frequency questionnaire. Information on smoking and physical activity was obtained by questionnaire.

Results

Intakes of all nutrients, corrected for energy intake, and all lifestyle characteristics except sleep duration were similar in biological children and their parents. As compared with their parents, adopted children had significantly different energy, protein, and calcium intakes and physical activity levels. In a regression model, BMD z scores of adopted children and their parents were significantly inversely associated at the spine and total femur, whereas BMD z scores of biological children and their parents were significantly positively associated at all measurement sites. The greatest proportion of total variance in BMD was accounted for by calcium intake among adopted children and by parental BMD among biological children.

Conclusions

For some lifestyle characteristics and nutrient intakes, the differences between parents and children were more obvious among adoptive families than among biological families. The most important lifestyle predictor of bone density was calcium intake.Key words: bone mineral density, adopted children, lifestyle, heredity, nutrition     

Engineered retroviral virus-like particles for receptor targeting

Retroviral gag proteins, as well as fragments minimally containing the capsid (CA) and nucleocapsid (NC) subunits of Gag, are able to spontaneously assemble into virus-like particles (VLPs). This occurs in mammalian and bacterial cells as well as in in vitro systems. In every circumstance, nucleic acids are incorporated into the forming particles. Here, we took advantage of an in vitro system for the generation of non-enveloped Mason-Pfizer monkey virus (M-PMV) VLPs derived from a self-assembling CA-NC subunit of Gag. These VLPs were modified through N-terminal extension of CA-NC with short oligopeptides that, after the assembly process, were exposed on the surface of VLPs. The employed N-terminal modifications allowed specific interaction with target cells expressing prostate-specific membrane antigen. Using this system, we were able to incorporate selected siRNA into forming VLPs and deliver it into the cytosol of target cells. In comparison with other viral vectors designed for targeted transgene delivery, this M-PMV VLP system represents the lowest risk of generating virus-associated pathology, as the VLPs do not contain any viral coding sequences and are formed in a cell-free system.