Feminizing effects of ethinylestradiol in roach (Rutilus rutilus) populations with different estrogenic pollution exposure histories.

Experimental exposures aimed at assessing the risks posed by estrogens in waste-water treatment work (WwTW) effluents to fish populations have rarely considered whether populations differ in their sensitivity to estrogenic compounds. This is despite evidence that selection at genes involved in the estrogen response has occurred in wild populations, and evidence that genotype can influence estrogen-response. In this study we compare the effects of a two-year exposure to a low measured concentration (1.3 ng/L) of ethinylestradiol (EE2) on the sexual development of roach (Rutilus rutilus) whose parental generation was sampled from two river stretches heavily contaminated with WwTW effluent and from two without any known WwTW effluent contamination. Exposure to EE2 significantly reduced the proportion of genetic males and induced a range of feminized phenotypes in males. Significantly, exposure also increased the proportion of genetic females with vitellogenic oocytes from 51 to 96%, raising the possibility that estrogen pollution could impact populations of annually spawning fish species through advancing female reproduction by at least a year. However, there was no evidence that river origin affected sensitivity to estrogens in either sex. Thus, we conclude that chronic exposure to low level EE2 has reproductive health outcomes for both male and female roach, but we find no evidence that the nature or magnitude of the response is affected by the population origin.

A Prosthetic Shank With Adaptable Torsion Stiffness and Foot Alignment.

Torsion adapters in lower limb prostheses aim to increase comfort, mobility and health of users by allowing rotation in the transversal plane. A preliminary study with two transtibial amputees indicated correlations between torsional stiffness and foot alignment to increase comfort and stability of the user depending on the gait situation and velocity. This paper presents the design and proof-of-concept of an active, bio-inspired prosthetic shank adapter and a novel approach to create a user-specific human-machine interaction through adapting the device's properties. To provide adequate support, load data and subjective feedback of subjects are recorded and analyzed regarding defined gait situations. The results are merged to an user individual preference-setting matrix to select optimal parameters for each gait situation and velocity. A control strategy is implemented to render the specified desired torsional stiffness and transversal foot alignment values to achieve situation-dependent adaptation based on the input of designed gait detection algorithms. The proposed parallel elastic drive train mimics the functions of bones and muscles in the human shank. It is designed to provide the desired physical human-machine interaction properties along with optimized actuator energy consumption. Following test bench verification, trials with five participants with lower limb amputation at different levels are performed for basic validation. The results suggest improved movement support in turning maneuvers. Subjective user feedback confirmed a noticeable reduction of load at the stump and improved ease of turning.

Exchange protein directly activated by cyclic AMP (EPAC) activation reverses neutrophil dysfunction induced by ß2-agonists, corticosteroids, and critical illness.

BACKGROUND: Neutrophils play a role in the pathogenesis of asthma, chronic obstructive pulmonary disease, and pulmonary infection. Impaired neutrophil phagocytosis predicts hospital-acquired infection. Despite this, remarkably few neutrophil-specific treatments exist. OBJECTIVES: We sought to identify novel pathways for the restoration of effective neutrophil phagocytosis and to activate such pathways effectively in neutrophils from patients with impaired neutrophil phagocytosis. METHODS: Blood neutrophils were isolated from healthy volunteers and patients with impaired neutrophil function. In healthy neutrophils phagocytic impairment was induced experimentally by using ß2-agonists. Inhibitors and activators of cyclic AMP (cAMP)-dependent pathways were used to assess the influence on neutrophil phagocytosis in vitro. RESULTS: ß2-Agonists and corticosteroids inhibited neutrophil phagocytosis. Impairment of neutrophil phagocytosis by ß2-agonists was associated with significantly reduced RhoA activity. Inhibition of protein kinase A (PKA) restored phagocytosis and RhoA activity, suggesting that cAMP signals through PKA to drive phagocytic impairment. However, cAMP can signal through effectors other than PKA, such as exchange protein directly activated by cyclic AMP (EPAC). An EPAC-activating analog of cAMP (8CPT-2Me-cAMP) reversed neutrophil dysfunction induced by ß2-agonists or corticosteroids but did not increase RhoA activity. 8CPT-2Me-cAMP reversed phagocytic impairment induced by Rho kinase inhibition but was ineffective in the presence of Rap-1 GTPase inhibitors. 8CPT-2Me-cAMP restored function to neutrophils from patients with known acquired impairment of neutrophil phagocytosis. CONCLUSIONS: EPAC activation consistently reverses clinical and experimental impairment of neutrophil phagocytosis. EPAC signals through Rap-1 and bypasses RhoA. EPAC activation represents a novel potential means by which to reverse impaired neutrophil phagocytosis.

Mean arterial blood pressure and the assessment of acutely ill patients.

This article discusses the role of vital sign data collection in the acute setting when assessing patients at risk of or actually clinically deteriorating. Specifically, the article focuses on explaining the important concepts of mean arterial blood pressure and pulse pressure as indicators of clinical deterioration.