Uptake, accumulation and metabolization of the antidepressant fluoxetine by Mytilus galloprovincialis

Fluoxetine, a selective serotonin re-uptake inhibitor (SSRI) antidepressant, is among the most prescribed pharmaceutical active substances worldwide. This study aimed to assess its accumulation and metabolization in the mussel Mytillus galloprovincialis, considered an excellent sentinel species for traditional and emerging pollutants. Mussels were collected from Ria Formosa Lagoon, Portugal, and exposed to a nominal concentration of fluoxetine (75 ng L-1) for 15 days. Approximately 1 g of whole mussel soft tissues was extracted with acetonitrile:formic acid, loaded into an Oasis MCX cartridge, and fluoxetine analysed by liquid chromatography with tandem mass spectrometry (LC-MSn). After 3 days of exposure, fluoxetine was accumulated in 70% of the samples, with a mean of 2.53 ng g(-1) dry weight (d.w.) and norfluoxetine was only detected in one sample (10%), at 3.06 ng g(-1) d.w. After 7 days of exposure, the accumulation of fluoxetine and norfluoxetine increased up to 80 and 50% respectively, and their mean accumulated levels in mussel tissues were up to 4.43 and 2.85 ng g(-1) d.w., respectively. By the end of the exposure period (15 days), both compounds were detected in 100% of the samples (mean of 9.31 and 11.65 ng g(-1) d.w., respectively). Statistical analysis revealed significant accumulation differences between the 3rd and 15th day of exposure for fluoxetine, and between the 3rd and 7th against the 15th day of exposure for norfluoxetine. These results suggest that the fluoxetine accumulated in mussel tissues is likely to be metabolised into norfluoxetine with the increase of the time of exposure, giving evidence that at these realistic environmental concentrations, toxic effects of fluoxetine in mussel tissues may occur. (C) 2016 Elsevier Ltd. All rights reserved

Mechanisms Driving the Effect of Weight Loss on Arterial Stiffness

Aims Arterial stiffness decreases with weight loss in overweight and obese adults, but the mechanisms by which this occurs are poorly understood. We aimed to elucidate these mechanisms. Methods We evaluated carotid-femoral pulse wave velocity (cfPWV), a measure of aortic stiffness, and brachial-ankle pulse wave velocity (baPWV), a mixed measure of central and peripheral arterial stiffness, in 344 young adults (mean age 38 yrs, mean body mass index (BMI) 32.9 kg/m2, 23% male) at baseline, 6 and 12 months in a behavioral weight loss intervention. Linear mixed effects models were used to evaluate associations between weight loss and arterial stiffness and to examine the degree to which improvements in obesity-related factors explained these associations. Pattern-mixture models using indicator variables for dropout pattern and Markov Chain Monte Carlo multiple imputation were used to evaluate the influence of different missing data assumptions. Results At 6 months (7% mean weight loss from baseline), there was a statistically significant median decrease of 47.5 cm/s (interquartile range (IQR) -44.5, 148) in cfPWV (p<0.0001) and a mean decrease of 11.7 cm/s (standard deviation (SD) 91.4) in baPWV (p=0.049). At 12 months (6% mean weight loss from baseline) only cfPWV remained statistically significantly reduced from baseline (p=0.02). Change in BMI (p=0.01) was statistically significantly positively associated with change in cfPWV after adjustment for changes in mean arterial pressure (MAP) or any other measured obesity-related factor. Common carotid artery diameter (p=0.003) was associated and heart rate (p=0.08) and MAP (p=0.07) marginally associated longitudinally with cfPWV. Reductions in heart rate (p<0.0001) and C-reactive protein (p=0.02) were associated with reduced baPWV, and each removed the statistical significance of the effect of weight loss on baPWV. Pattern-mixture modeling revealed several differences between completers and non-completers in the models for cfPWV, but marginal parameter estimates changed little from the original models for either PWV measure. Conclusions The public health importance of this thesis is that firstly, weight loss improves arterial stiffness in overweight and obese young adults. Secondly, its effect on baPWV may be explained by concurrent reductions in heart rate and inflammation. Missing data did not appear to bias these results

Total and high-molecular-weight adiponectin levels in relation to insulin resistance among overweight/obese adults.

Objective: To determine whether baseline levels or intervention-associated changes in total and high molecular weight (HMW) adiponectin levels were associated with insulin resistance after six months of behavioral treatment for weight loss. Design: An ancillary study to a behavioral weight loss trial; the intervention was delivered in group sessions. Methods: Participants included 143 overweight/obese adults with a mean BMI of 33.7 kg/m2. The sample was 88% female, 67% white, and 44.2 ± 8.5 years old. Circulating adiponectin levels (total and HMW) and the homeostasis model assessment (HOMA) of insulin resistance were measured and evaluated. Results: At baseline, there was significant inverse associations between total adiponectin and HOMA (p < 0.001) and between HMW adiponectin and HOMA (p < 0.001) independent of weight. At 6-mo, there was a 17% improvement in HOMA, 8% increase in total adiponectin, 17% increase in HMW adiponectin levels, and 8.72% weight loss (p's for all< 0.001). There was also a significant inverse association between changes in total adiponectin and HOMA (p = 0.04) that was independent of baseline weight and weight loss. In contrast, the association between changes in HMW adiponectin and HOMA was attenuated after adjustment for weight loss. Conclusions: An increased level of total adiponectin was associated with improved insulin sensitivity, regardless of baseline weight and weight loss. However, baseline total and HMW adiponectin levels were more strongly associated with HOMA than changes in these measures at six months. HMW adiponectin level was not related more closely to insulin resistance than total adiponectin level

Peer Support Specialists and Service Users’ Perspectives on privacy, confidentiality, and security of digital mental health

As the digitalization of mental health systems progresses, the ethical and social debate on the use of these mental health technologies has seldom been explored among end-users. This article explores how service users (e.g., patients and users of mental health services) and peer support specialists understand and perceive issues of privacy, confidentiality, and security of digital mental health interventions. Semi-structured qualitative interviews were conducted among service users (n = 17) and peer support specialists (n = 15) from a convenience sample at an urban community mental health center in the United States. We identified technology ownership and use, lack of technology literacy including limited understanding of privacy, confidentiality, and security as the main barriers to engagement among service users. Peers demonstrated a high level of technology engagement, literacy of digital mental health tools, and a more comprehensive awareness of digital mental health ethics. We recommend peer support specialists as a potential resource to facilitate the ethical engagement of digital mental health interventions for service users. Finally, engaging potential end-users in the development cycle of digital mental health support platforms and increased privacy regulations may lead the field to a better understanding of effective uses of technology for people with mental health conditions. This study contributes to the ongoing debate of digital mental health ethics, data justice, and digital mental health by providing a first-hand experience of digital ethics from end-users’ perspectives.publishedVersio

Complementary, Semi-automated Methods for Creating Multi-dimensional, PEG-based Biomaterials

Tunable biomaterials that mimic selected features of the extracellular matrix (ECM), such as its stiffness, protein composition, and dimensionality, are increasingly popular for studying how cells sense and respond to ECM cues. In the field, there exists a significant trade-off for how complex and how well these biomaterials represent the in vivo microenvironment, versus how easy they are to make and how adaptable they are to automated fabrication techniques. To address this need to integrate more complex biomaterials design with high-throughput screening approaches, we present several methods to fabricate synthetic biomaterials in 96-well plates and demonstrate that they can be adapted to semiautomated liquid handling robotics. These platforms include 1) glass bottom plates with covalently attached ECM proteins, and 2) hydrogels with tunable stiffness and protein composition with either cells seeded on the surface, or 3) laden within the three-dimensional hydrogel matrix. This study includes proof-of-concept results demonstrating control over breast cancer cell line phenotypes via these ECM cues in a semi-automated fashion. We foresee the use of these methods as a mechanism to bridge the gap between high-throughput cell-matrix screening and engineered ECM-mimicking biomaterials

Total and high-molecular-weight adiponectin levels in relation to insulin resistance among overweight/obese adults

Objective: To determine whether baseline levels or intervention-associated changes in total and high molecular weight (HMW) adiponectin levels were associated with insulin resistance after six months of behavioral treatment for weight loss.Design: An ancillary study to a behavioral weight loss trial; the intervention was delivered in group sessions.Methods: Participants included 143 overweight/obese adults with a mean BMI of 33.7 kg/m2. The sample was 88% female, 67% white, and 44.2 ± 8.5 years old. Circulating adiponectin levels (total and HMW) and the homeostasis model assessment (HOMA) of insulin resistance were measured and evaluated.Results: At baseline, there was significant inverse associations between total adiponectin and HOMA (p &lt; 0.001) and between HMW adiponectin and HOMA (p &lt; 0.001) independent of weight. At 6-mo, there was a 17% improvement in HOMA, 8% increase in total adiponectin, 17% increase in HMW adiponectin levels, and 8.72% weight loss (p's for all&lt; 0.001). There was also a significant inverse association between changes in total adiponectin and HOMA (p = 0.04) that was independent of baseline weight and weight loss. In contrast, the association between changes in HMW adiponectin and HOMA was attenuated after adjustment for weight loss.Conclusions: An increased level of total adiponectin was associated with improved insulin sensitivity, regardless of baseline weight and weight loss. However, baseline total and HMW adiponectin levels were more strongly associated with HOMA than changes in these measures at six months. HMW adiponectin level was not related more closely to insulin resistance than total adiponectin level.

Applicability of Drug Response Metrics for Cancer Studies using Biomaterials

Bioengineers have built models of the tumour microenvironment (TME) in which to study cell–cell interactions, mechanisms of cancer growth and metastasis, and to test new therapies. These models allow researchers to culture cells in conditions that include features of the in vivo TME implicated in regulating cancer progression, such as extracellular matrix (ECM) stiffness, integrin binding to the ECM, immune and stromal cells, growth factor and cytokine depots, and a three-dimensional geometry more representative of the in vivo TME than tissue culture polystyrene (TCPS). These biomaterials could be particularly useful for drug screening applications to make better predictions of efficacy, offering better translation to preclinical models and clinical trials. However, it can be challenging to compare drug response reports across different biomaterial platforms in the current literature. This is, in part, a result of inconsistent reporting and improper use of drug response metrics, and vast differences in cell growth rates across a large variety of biomaterial designs. This study attempts to clarify the definitions of drug response measurements used in the field, and presents examples in which these measurements can and cannot be applied. We suggest as best practice to measure the growth rate of cells in the absence of drug, and follow our ‘decision tree’ when reporting drug response metrics

Hyphema. Part II. Diagnosis and Treatment

The clinical appearance of hyphema is variable and is influenced by the volume of blood and the amount of time erythrocytes are present in the anterior chamber. When hyphema is evident, a complete history should be obtained and a thorough physical examination performed to direct the initial selection of diagnostic tests. Secondary complications of hyphema include glaucoma, synechiae, cataract formation, blood-staining of the cornea, and blindness. Frequent measurement of intraocular pressure is recommended. The two primary management issues in animals with hyphema are prevention of secondary hemorrhage (by treating the underlying disease) and control of secondary glaucoma

Hyphema. Part I. Pathophysiologic Considerations

Hemorrhage in the anterior chamber of the eye, or hyphema, results from a breakdown of the blood-ocular barrier (BOB) and is frequently associated with inflammation of the iris, ciliary body, or retina. Hyphema can also occur by retrograde blood flow into the anterior chamber via the aqueous humor drainage pathways without BOB breakdown. Hyphema attributable to blunt or perforating ocular trauma is more common than that resulting from endogenous causes. When trauma has been eliminated as a possible cause, it is prudent to assume that every animal with hyphema has a serious systemic disease until proven otherwise