Socioeconomic inequalities in health among Swedish adolescents - adding the subjective perspective

Abstract Background Socioeconomic inequalities in adolescent health predict future inequalities in adult health. Subjective measures of socioeconomic status (SES) may contribute with an increased understanding of these inequalities. The aim of this study was to investigate socioeconomic health inequalities using both a subjective and an objective measure of SES among Swedish adolescents. Method Cross-sectional HBSC-data from 2002 to 2014 was used with a total sample of 23,088 adolescents aged 11–15 years. Three measures of self-rated health (dependent variables) were assessed: multiple health complaints, life satisfaction and health perception. SES was measured objectively by the Family Affluence Scale (FAS) and subjectively by “perceived family wealth” (independent variables). The trend for health inequalities was investigated descriptively with independent t-tests and the relationship between independent and dependent variables was investigated with multiple logistic regression analysis. Gender, age and survey year was considered as possible confounders. Results Subjective SES was more strongly related to health outcomes than the objective measure (FAS). Also, the relation between FAS and health was weakened and even reversed (for multiple health complaints) when subjective SES was tested simultaneously in regression models (FAS OR: 1.03, CI: 1.00;1.06 and subjective SES OR: 0.66, CI: 0.63;0.68). Conclusions The level of socioeconomic inequalities in adolescent health varied depending on which measure that was used to define SES. When focusing on adolescents, the subjective appraisals of SES is important to consider because they seem to provide a stronger tool for identifying inequalities in health for this group. This finding is important for policy makers to consider given the persistence of health inequalities in Sweden and other high-income countries

Cellular localization, accumulation and trafficking of double-walled carbon nanotubes in human prostate cancer cells

Carbon nanotubes (CNTs) are at present being considered as potential nanovectors with the ability to deliver therapeutic cargoes into living cells. Previous studies established the ability of CNTs to enter cells and their therapeutic utility, but an appreciation of global intracellular trafficking associated with their cellular distribution has yet to be described. Despite the many aspects of the uptake mechanism of CNTs being studied, only a few studies have investigated internalization and fate of CNTs inside cells in detail. In the present study, intracellular localization and trafficking of RNA-wrapped, oxidized double-walled CNTs (oxDWNT–RNA) is presented. Fixed cells, previously exposed to oxDWNT–RNA, were subjected to immunocytochemical analysis using antibodies specific to proteins implicated in endocytosis; moreover cell compartment markers and pharmacological inhibitory conditions were also employed in this study. Our results revealed that an endocytic pathway is involved in the internalization of oxDWNT–RNA. The nanotubes were found in clathrin-coated vesicles, after which they appear to be sorted in early endosomes, followed by vesicular maturation, become located in lysosomes. Furthermore, we observed co-localization of oxDWNT–RNA with the small GTP-binding protein (Rab 11), involved in their recycling back to the plasma membrane via endosomes from the trans-golgi network

Case Report: Dual nebulised antibiotics among adults with cystic fibrosis and chronic Pseudomonas infection [version 2; referees: 1 approved, 2 approved with reservations]

Pulmonary exacerbations in adults with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa (Psae) infection are usually treated with dual intravenous antibiotics for 14 days, despite the lack of evidence for best practice. Intravenous antibiotics are commonly associated with various systemic adverse effects, including renal failure and ototoxicity. Inhaled antibiotics are less likely to cause systematic adverse effects, yet can achieve airway concentrations well above conventional minimum inhibitory concentrations. Typically one inhaled antibiotic is used at a time, but dual inhaled antibiotics (i.e. concomitant use of two different inhaled antibiotics) may have synergistic effect and achieve better results in the treatment of exacerbations. We presented anecdotal evidence for the use of dual inhaled antibiotics as an acute treatment for exacerbations, in the form of a case report. A female in her early thirties with CF and chronic Psae infection improved her FEV1 by 5% and 2% with two courses of dual inhaled antibiotics to treat exacerbations in 2016. In contrast, her FEV1 changed by 2%, –2%, 0% and 2%, respectively, with four courses of dual intravenous antibiotics in 2016. Baseline FEV1 was similar prior to all six courses of treatments. The greater FEV1 improvements with dual inhaled antibiotics compared to dual intravenous antibiotics suggest the potential role of using dual inhaled antibiotics to treat exacerbations among adults with CF and chronic Psae infection, especially since a greater choice of inhaled anti-pseudomonal antibiotics is now available. A previous study in 1985 has looked at the concomitant administration of inhaled tobramycin and carbenicillin, by reconstituting antibiotics designed for parenteral administration. To our knowledge, this is the first literature to describe the concomitant use of two different antibiotics specifically developed for delivery via the inhaled route

Therapeutic opportunities and challenges in targeting the orphan G protein-coupled receptor GPR35

GPR35 is a class A, rhodopsin-like G protein-coupled receptor (GPCR) first identified more than 20 years ago. In the intervening period identification of strong expression in the lower intestine and colon, as well as in a variety of immune cells including monocytes and a variety of dendritic cells, and in dorsal root ganglia, has suggested potential therapeutic opportunities in targeting this receptor in a range of conditions. GPR35 is, however, unusual in a variety of ways that challenge routes to translation. These include that although a substantial range and diversity of endogenous ligands have been suggested as agonist partners for this receptor it officially remains defined as an ‘orphan’ GPCR; that humans express two distinct protein isoform sequences whilst rodents express only a single form, and that the pharmacology of the human and rodent orthologues of GPR35 is very distinct, with variation between rat and mouse GPR35 as marked as between either of these species and the human forms. 2 Herein we provide perspectives on each of the topics above as well as suggesting ways to overcome the challenges currently hindering potential translation. These include better understanding of the extent and molecular basis for species selective GPR35 pharmacology and the production of novel mouse models in which both ‘on-target’ and ‘off-target’ effects of presumptive GPR35 ligands can be better defined as well as clear understanding in human of isoform expression profile and its significance at both tissue and individual cell level

Influence of packing density and surface roughness of vertically-aligned carbon nanotubes on adhesive properties of gecko-inspired mimetics.

We have systematically studied the macroscopic adhesive properties of vertically aligned nanotube arrays with various packing density and roughness. Using a tensile setup in shear and normal adhesion, we find that there exists a maximum packing density for nanotube arrays to have adhesive properties. Too highly packed tubes do not offer intertube space for tube bending and side-wall contact to surfaces, thus exhibiting no adhesive properties. Likewise, we also show that the surface roughness of the arrays strongly influences the adhesion properties and the reusability of the tubes. Increasing the surface roughness of the array strengthens the adhesion in the normal direction, but weakens it in the shear direction. Altogether, these results allow progress toward mimicking the gecko's vertical mobility.The authors acknowledge funding from the EC project Technotubes.This is the accepted manuscript. The final version is available at http://pubs.acs.org/doi/abs/10.1021/am507822b

Forging a Path Toward Health Equity in 2040

Dramatic shifts in the demographic makeup of the U.S. population in 2040 will pose new challenges and opportunities for policy makers, researchers, and community members working to address health and health care inequities. Traditional approaches utilizing a health disparities framework may not be enough to address the health needs of an increasingly diverse and multiracial population of Asian Americans and Native Hawaiians and Pacific Islanders (NHPIs). This article provides an overview of the current and projected health and health care needs of Asian Americans and NHPIs in 2040, and proposes new policy solutions and frameworks for addressing these complex needs

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.Postprint (published version

Receptor selectivity between the G proteins Gα12 and Gα13 is defined by a single leucine-to-isoleucine variation

Despite recent advances in structural definition of GPCR–G protein complexes, the basis of receptor selectivity between G proteins remains unclear. The Gα12 and Gα13 subtypes together form the least studied group of heterotrimeric G proteins. G protein–coupled receptor 35 (GPR35) has been suggested to couple efficiently to Gα13 but weakly to Gα12. Using combinations of cells genome-edited to not express G proteins and bioluminescence resonance energy transfer–based sensors, we confirmed marked selectivity of GPR35 for Gα13. Incorporating Gα12/Gα13 chimeras and individual residue swap mutations into these sensors defined that selectivity between Gα13 and Gα12 was imbued largely by a single leucine-to-isoleucine variation at position G.H5.23. Indeed, leucine could not be substituted by other amino acids in Gα13 without almost complete loss of GPR35 coupling. The critical importance of leucine at G.H5.23 for GPR35–G protein interaction was further demonstrated by introduction of this leucine into Gαq, resulting in the gain of coupling to GPR35. These studies demonstrate that Gα13 is markedly the most effective G protein for interaction with GPR35 and that selection between Gα13 and Gα12 is dictated largely by a single conservative amino acid variation.—Mackenzie, A. E., Quon, T., Lin, L.-C., Hauser, A. S., Jenkins, L., Inoue, A., Tobin, A. B., Gloriam, D. E., Hudson, B. D., Milligan, G. Receptor selectivity between the G proteins Gα12 and Gα13 is defined by a single leucine-to-isoleucine variation

Musical components important for the Mozart K448 effect in epilepsy

There is growing evidence for the efficacy of music, specifically Mozart’s Sonata for Two Pianos in D Major (K448), at reducing ictal and interictal epileptiform activity. Nonetheless, little is known about the mechanism underlying this beneficial “Mozart K448 effect” for persons with epilepsy. Here, we measured the influence that K448 had on intracranial interictal epileptiform discharges (IEDs) in sixteen subjects undergoing intracranial monitoring for refractory focal epilepsy. We found reduced IEDs during the original version of K448 after at least 30-s of exposure. Nonsignificant IED rate reductions were witnessed in all brain regions apart from the bilateral frontal cortices, where we observed increased frontal theta power during transitions from prolonged musical segments. All other presented musical stimuli were associated with nonsignificant IED alterations. These results suggest that the “Mozart K448 effect” is dependent on the duration of exposure and may preferentially modulate activity in frontal emotional networks, providing insight into the mechanism underlying this response. Our findings encourage the continued evaluation of Mozart’s K448 as a noninvasive, non-pharmacological intervention for refractory epilepsy

Investigation of wet milling and indirect ultrasound as means for controlling nucleation in the continuous crystallization of an active pharmaceutical ingredient

This study compares the use of wet milling and indirect ultrasound for promoting nucleation and controlling the particle size during the continuous crystallization of a hard-to-nucleate active pharmaceutical ingredient (API). Both an immersion and an external wet mill installed on a recirculation loop were investigated. It was found that all methodologies significantly improved the nucleation kinetics, and the effects of key process parameters (e.g., mill speed, temperature, and ultrasound intensity) on particle size were experimentally investigated. A minimum d50 of 27 and 36.8 μm was achieved when using the wet mill and ultrasound, respectively. The effectiveness of wet milling was demonstrated in a three-stage mixed suspension mixed product removal continuous crystallization of the API that was operated continuously for 12 h (eight residence times), achieving a steady state with minimal fouling. Strategies for improving the overall robustness of the setup in routine manufacturing are discussed