Multidisciplinary Consideration of Potential Pathophysiologic Mechanisms of Paradoxical Erythema with Topical Brimonidine Therapy.

Rosacea is a chronic inflammatory disease with transient and non-transient redness as key characteristics. Brimonidine is a selective α2-adrenergic receptor (AR) agonist approved for persistent facial erythema of rosacea based on significant efficacy and good safety data. The majority of patients treated with brimonidine report a benefit; however, there have been sporadic reports of worsening erythema after the initial response. A group of dermatologists, receptor physiology, and neuroimmunology scientists met to explore potential mechanisms contributing to side effects as well as differences in efficacy. We propose the following could contribute to erythema after application: (1) local inflammation and perivascular inflammatory cells with abnormally functioning ARs may lead to vasodilatation; (2) abnormal saturation and cells expressing different AR subtypes with varying ligand affinity; (3) barrier dysfunction and increased skin concentrations of brimonidine with increased actions at endothelial and presynaptic receptors, resulting in increased vasodilation; and (4) genetic predisposition and receptor polymorphism(s) leading to different smooth muscle responses. Approximately 80% of patients treated with brimonidine experience a significant improvement without erythema worsening as an adverse event. Attention to optimizing skin barrier function, setting patient expectations, and strategies to minimize potential problems may possibly reduce further the number of patients who experience side effects.FundingGalderma International S.A.S., Paris, France

Inappropriate flushing of menstrual sanitary products

This paper explores the disposal strategies of menstrual sanitary products through in-depth semi-structured interviews of women aged 18-30 years. There have been many educational campaigns to encourage solid stream waste disposal, however inappropriate disposal and blockages are still a major problem for the water industry. Whilst there have been quantitative studies exploring self-reporting of flushing norms, there is evidence to suggest these results may not take into account the complex set of socio-cultural factors associated with menstrual product disposal. Bridging this gap, our interviews found that although all participants had a desire to responsibly dispose, their ability to utilise solid waste streams or to minimise waste by using reusable products was not always possible because they felt, to some degree, restricted by the wider societal requirements for discretion and the design, accessibility and availability of bins and bathroom facilities. Based on these findings Industry recommendations are suggested

The effects of food rationing on phenotypic plasticity in reproductive resource allocation in female wild-type zebrafish, Danio rerio

Any resources obtained by an organism must be divided between life history components, namely growth, reproduction and survival. Resources are limited, thus creating trade-offs between competing traits. One trade-off is the relationship between the size and the number of offspring (fecundity) produced by a mother. Although adaptive phenotypic plasticity in this trade-off has been demonstrated across the Animal Kingdom, understanding of the mechanisms behind this is lacking. For example, female zebrafish (Danio rerio) subjected to different feeding regimes have shown this phenotypic plasticity, but studies have not determined the mediators of this change. This thesis aimed to examine the phenotypic plasticity in resource allocation to reproduction in wild-type zebrafish and elucidate mechanisms allowing the change. Female zebrafish were fed either 1.5% (Low) or 3% (High) of body weight daily and phenotypic changes in fecundity, offspring size and gene expression of five candidate genes in the ovary were evaluated. Representative ovary samples were also analysed by RNA-Seq. There were trends for increases in lrp8 and esr2a mRNA expression levels in the ovaries of the food-limited females when compared with food-abundant females. This supported previous literature demonstrating increases in vitellogenin in larger eggs. In the food-abundant females, there was an increase in fshr mRNA expression levels. This could be a mechanism to increase fecundity, through increased follicles entering vitellogenesis. A second experiment was performed to assess the sensitivity and timing of the resource allocation decisions. Female zebrafish were exposed to an initial feeding regime for four weeks and then switched to the other feeding regime for another four weeks. These females were analysed for differences in resource allocation and the trade-off between follicle size and reproductive investment was analysed regardless of feeding regime. Across both experiments, differences in phenotype were hard to discern due to the effects of maternal condition. There were marked differences in females within the same tanks, possibly due to dominance effects, and this may have obscured the effects of the individual feeding regimes. Overall, there was no adaptive phenotypic plasticity in offspring size or offspring number evident in the experiments presented. Future gene expression studies on females clearly demonstrating differences in phenotype are necessary

A randomised crossover trial comparing Thai and Swedish massage for fatigue and depleted energy

SUMMARY\ud Background\ud The aim of this study was to compare the efficacy and social constructions of Thai\ud massage (TM) and Swedish massage (SM) for patients experiencing fatigue or\ud depleted energy.\ud Method\ud Twenty participants were randomised to receive three once-weekly TM treatments\ud and three once-weekly SM treatments, with crossover after three massages.\ud Symptom checklists were administered at three time points and included\ud Activation-Deactivation Adjective Check List and VAS Scale. Qualitative data\ud were collected through semi-structured interviews and participants’ diary entries.\ud Results\ud Both massage types enhanced physical, emotional and mental wellbeing through\ud improved sleep, relaxation, relief of stress and relief of muscular tension. TM\ud alone showed specific energising and psychological stimulation results, along with\ud carry-over effect and longer lasting benefits. Ninety-five percent of participants\ud found relief from their initial reason presenting symptoms\ud Conclusion\ud TM or SM can relieve symptoms of fatigue or low energy by releasing stress,\ud promoting relaxation, relieving muscular aches and pains and improving energy.\ud SM results in a larger effect in relaxation and improved sleep whereas TM results\ud in a larger effect in energising, rejuvenating and mentally stimulating effects.\ud Keywords: Complementary Therapies; Therapy, Soft Tissue; Massage; Cross-\ud Over Studie

Stressful life-events exposure is associated with 17-year mortality, but it is health-related events that prove predictive

Objectives Despite the widely-held view that psychological stress is a major cause of poor health, few studies have examined the relationship between stressful life-events exposure and death. The present analyses examined the association between overall life-events stress load, health-related and health-unrelated stress, and subsequent all-cause mortality.\ud \ud Design This study employed a prospective longitudinal design incorporating time-varying covariates.\ud \ud Methods Participants were 968 Scottish men and women who were 56 years old. Stressful life-events experience for the preceding 2 years was assessed at baseline, 8–9 years and 12–13 years later. Mortality was tracked for the subsequent 17 years during which time 266 participants had died. Cox's regression models with time-varying covariates were applied. We adjusted for sex, occupational status, smoking, BMI, and systolic blood pressure.\ud \ud Results Overall life-events numbers and their impact scores at the time of exposure and the time of assessment were associated with 17-year mortality. Health-related event numbers and impact scores were strongly predictive of mortality. This was not the case for health-unrelated events.\ud \ud Conclusions The frequency of life-events and the stress load they imposed were associated with all-cause mortality. However, it was the experience and impact of health-related, not health-unrelated, events that proved predictive. This reinforces the need to disaggregate these two classes of exposures in studies of stress and health outcomes.\u

Assessment of source and treated water quality in seven drinking water treatment plants by in vitro bioassays – Oxidative stress and antiandrogenic effects after artificial infiltration.

Drinking water quality and treatment efficacy was investigated in seven drinking water treatment plants (DWTPs), using water from the river Göta Älv, which also is a recipient of treated sewage water. A panel of cell-based bioassays was used, including measurements of receptor activity of aryl hydrocarbon (AhR), estrogen (ER), androgen (AR), peroxisome proliferator-activated receptor alpha (PPARα) as well as induction of oxidative stress (Nrf2) and micronuclei formation. Grab water samples were concentrated by solid phase extraction (SPE) and water samples were analyzed at a relative enrichment factor of 50. High activities of AhR, ER and AR antagonism were present in WWTP outlets along the river. Inlet water from the river exhibited AhR and AR antagonistic activities. AhR activity was removed by DWTPs using granulated activated carbon (GAC) and artificial infiltration. AR antagonistic activity was removed by the treatment plants, except the artificial infiltration plant, which actually increased the activity. Furthermore, treated drinking water from the DWTP using artificial infiltration exhibited high Nrf2 activity, which was not found in any of the other water samples. Nrf2 activity was found in water from eight of the 13 abstraction wells, collecting water from the artificial infiltration. No genotoxic activity was detected at non-cytotoxic concentrations. No Nrf2 or AR antagonistic activities were detected in the inlet or outlet water after the DWTP had been replaced by a new plant, using membrane ultrafiltration and GAC. Neither target chemical analysis, nor chemical analysis according to the drinking water regulation, detected any presence of chemicals, which could be responsible of the prominent effects on oxidative stress and AR antagonistic activity in the drinking water samples. Thus, bioanalysis is a useful tool for detection of unknown hazards in drinking water and for assessment of drinking water treatments

The combination of Paclitaxel and Gefitinib inhibits endometrial cancer cells by inducing mitotic catastrophe: proof of principle for dual therapy in endometrial cancer

Serous uterine endometrial cancer is a lethal disease for which new therapeutic regimens are urgently needed. Combinations of chemotherapeutic agents and small molecule growth factor inhibitors have demonstrated activity in cancers from other sites. Our objective was to determine whether such a combination using Paclitaxel and Gefitinib could be active in serous endometrial cancer cells

State-Dependent Differences in Functional Connectivity in Young Children With Autism Spectrum Disorder

AbstractBackgroundWhile there is increasing evidence of altered brain connectivity in autism, the degree and direction of these alterations in connectivity and their uniqueness to autism has not been established. The aim of the present study was to compare connectivity in children with autism to that of typically developing controls and children with developmental delay without autism.MethodsWe assessed EEG spectral power, coherence, phase lag, Pearson and partial correlations, and epileptiform activity during the awake, slow wave sleep, and REM sleep states in 137 children aged 2 to 6years with autism (n=87), developmental delay without autism (n=21), or typical development (n=29).FindingsWe found that brain connectivity, as measured by coherence, phase lag, and Pearson and partial correlations distinguished children with autism from both neurotypical and developmentally delayed children. In general, children with autism had increased coherence which was most prominent during slow wave sleep.InterpretationFunctional connectivity is distinctly different in children with autism compared to samples with typical development and developmental delay without autism. Differences in connectivity in autism are state and region related. In this study, children with autism were characterized by a dynamically evolving pattern of altered connectivity