CYP4A1 antisense oligonucleotide reduces mesenteric vascular reactivity and blood pressure in SHR

The cytochrome P-450 4A (CYP4A)-derived arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) affects renal tubular and vascular functions and has been implicated in the control of arterial pressure. We examined the effect of antisense oligonucleotide (ODN) to CYP4A1, the low K(m) arachidonic acid omega-hydroxylating isoform, on vascular 20-HETE synthesis, vascular reactivity, and blood pressure in the spontaneously hypertensive rat (SHR). Administration of CYP4A1 antisense ODN decreased mean arterial blood pressure from 137 +/- 3 to 121 +/- 4 mmHg (P < 0.05) after 5 days of treatment, whereas treatment with scrambled antisense ODN had no effect. Treatment with CYP4A1 antisense ODN reduced the level of CYP4A-immunoreactive proteins along with 20-HETE synthesis in mesenteric arterial vessels. Mesenteric arteries from rats treated with antisense ODN exhibited decreased sensitivity to the constrictor action of phenylephrine (EC(50) 0.69 +/- 0.17 vs. 1.77 +/- 0.40 microM). Likewise, mesenteric arterioles from antisense ODN-treated rats revealed attenuation of myogenic constrictor responses to increases of transmural pressure. The decreased vascular reactivity and myogenic responses were reversible with the addition of 20-HETE. These data suggest that CYP4A1-derived 20-HETE facilitates myogenic constrictor responses in the mesenteric microcirculation and contributes to pressor mechanisms in SHR.     

Towards modelling the future risk of cyclone wave damage to the world's coral reefs

Tropical cyclones generate extreme waves that can damage coral reef communities. Recovery typically requires up to a decade, driving the trajectory of coral community structure. Coral reefs have evolved over millennia with cyclones. Increasingly, however, processes of recovery are interrupted and compromised by additional pressures (thermal stress, pollution, diseases, predators). Understanding how cyclones interact with other pressures to threaten coral reefs underpins spatial prioritization of conservation and management interventions. Models that simulate coral responses to cumulative pressures often assume that the worst cyclone wave damage occurs within ~100 km of the track. However, we show major coral loss at exposed sites up to 800 km from a cyclone that was both strong (high sustained wind speeds >=33 m/s) and big (widespread circulation >~300 km), using numerical wave models and field data from northwest Australia. We then calculate the return time of big and strong cyclones, big cyclones of any strength and strong cyclones of any size, for each of 150 coral reef ecoregions using a global data set of past cyclones from 1985 to 2015. For the coral ecoregions that regularly were exposed to cyclones during that time, we find that 75% of them were exposed to at least one cyclone that was both big and strong. Return intervals of big and strong cyclones are already less than 5 years for 13 ecoregions, primarily in the cyclone‐prone NW Pacific, and less than 10 years for an additional 14 ecoregions. We identify ecoregions likely at higher risk in future given projected changes in cyclone activity. Robust quantification of the spatial distribution of likely cyclone wave damage is vital not only for understanding past coral response to pressures, but also for predicting how this may change as the climate continues to warm and the relative frequency of the strongest cyclones rises.     

Adolescent Medicine: Attitudes,Training, and Experience Of Pediatric,Family Medicine,and Obstetric-Gynecology Residents

Purpose: Several studies have documented a deficiency in the delivery of preventive services to adolescents during physician visits in the United States. This study sought to assess and compare pediatric, family medicine (FM), and obstetrics and gynecology (OB/GYN) resident perceptions of their responsibility, training, and experience with providing comprehensive health care services to adolescents.Methods: A 57-item, close-ended survey was designed and administered to assess resident perceptions of the scope of their practice, training, and experience with providing adolescent health care across a series of health care categories.Results: Of the 87 respondents (31 OB/GYN, 29 FM, and 27 pediatric), most residents from all three fields felt that the full range of adolescent preventive and clinical services represented in the survey fell under their scope of practice. Residents from all three fields need more training and experience with mental health issues, referring teenagers to substance abuse treatment programs, and addressing physical and sexual abuse. In addition, OB-GYN residents reported deficiencies in training and experience regarding several preventive counseling and general health services, while pediatric residents reported deficiencies in training and experience regarding sexual health services.Conclusions: Our results indicate that at this time, residents from these three specialties are not optimally prepared to provide the full range of recommended preventive and clinical services to adolescents.