Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (~9 AM), ...potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1) platelet function and (2) platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise.
We studied 12 healthy adults (6 female) who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP) IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p ≤ 0.01). These circadian peaks occurred at a circadian phase corresponding to 8-9 AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8 PM). The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors.
These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans--independent of the sleep/wake cycle, other behavioral influences and the environment. The 9 AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous circadian influences on platelet function could contribute to the morning peak in adverse cardiovascular events as seen in many epidemiological studies.
In the novel coronavirus disease 2019 (COVID-19) pandemic, social distancing has been necessary to help prevent disease transmission. As a result, medical practices have limited access to in-person ...visits. This poses a challenge to maintain appropriate patient care while preventing a substantial backlog of patients once stay-at-home restrictions are lifted. In practices that are naïve to telehealth as an alternative option, providers and staff are experiencing challenges with telemedicine implementation. We aim to provide a comprehensive guide on how to rapidly integrate telemedicine into practice during a pandemic.
We built a toolkit that details the following 8 essential components to successful implementation of a telemedicine platform: provider and staff training, patient education, an existing electronic medical record system, patient and provider investment in hardware, billing and coding integration, information technology support, audiovisual platforms, and patient and caregiver participation.
Rapid integration of telemedicine in our practice was required to be compliant with our institution’s COVID-19 task force. Within 3 days of this declaration, our large specialty-care clinic converted to a telemedicine platform and we completed 638 visits within the first month of implementation.
Effective and efficient integration of a telemedicine program requires extensive staff and patient education, accessory platforms to facilitate video and audio communication, and adoption of new billing codes that are outlined in this toolkit.
Worldwide, roads are a main driver of deforestation and degradation as they increase forest access along the forest edge. In many tropical areas, unofficial roads go unreported and unrecorded, ...resulting in inaccurate estimates of intact forested areas. This is the case in central Sumatra, which boasts populations of critically endangered Sumatran elephants (Elephas maximus sumatrensis), tigers (Panthera tigris sumatrae) and other endemic flora and fauna that make the area globally unique. However, maps do not reflect the reality of forest loss in the area. Here we present new maps from 2002 and 2016 of digitized and ground-truthed roads in one of Sumatra's unique lowland tropical protected areas, Tesso Nilo National Park. Using our newly created roads dataset, we examine the distribution of forest with respect to distance to roads. Our data show >2,400 km of roads within the national park in 2016 -nearly a 10-fold increase from roads known in 2002. Most forest (82-99%) within Tesso Nilo falls within 100 m, 500 m, and 1000 m of road edges. Length of road increased 157% and road density increased from 1.06 km/km2 to 2.63 km/km2 from 2002-2016. Our results suggest that this endemic ecosystem is facing substantial threat from roads and their associated impacts. Without swift management action, such as road closures and increased enforcements by park management, this ecosystem, and its endemic wildlife, could be lost. It is imperative that protected areas worldwide more rigorously consider roads and road effects on ecosystem fragmentation in their conservation plans.
The central nervous system effects of oral contraceptives (OCs) are not well-documented. In a set of 3 studies, we investigated a specific cognitive function, mental rotation, in healthy women ...currently using OCs for contraceptive purposes (
n
= 201) and in medication-free controls not using OCs (
n
= 44). Mental rotation was measured using a well-standardized and extensively validated psychometric test, the Vandenberg Mental Rotations Test (MRT). In an initial study (Study 1), current OC users (
n
= 63) were tested during the active or inactive phases of the contraceptive cycle in a parallel-groups design. Studies 2 and 3 were based on an archival dataset (
n
= 201 current OC users) that consisted of data on the MRT collected in real-time over a 30-year period and compiled for purposes of the present work. The OCs were combined formulations containing ethinyl estradiol (10-35 ug/day) plus a synthetic progestin. All 4 families of synthetic progestins historically used in OCs were represented in the dataset. Cognitive performance was evaluated during either active OC use (‘active phase’) or during the washout week of the contraceptive cycle (‘inactive phase’) when OC steroids are not used. The results showed a significant phase-of-cycle (POC) effect. Accuracy on the MRT was mildly diminished during the active phase of OC use, while scores on verbal fluency and speeded motor tasks were modestly improved. The POC effect was most evident in women using OCs that contained first- or second-generation progestins (the estrane family of progestins or OCs containing levonorgestrel), but not in women using OCs containing recently developed progestins and lower doses of ethinyl estradiol. Using independently established ratings of the estrogenic, androgenic, and progestogenic intensities of the different OC formulations, each brand of OC was classified according to its distinct endocrine profile. Multiple regression revealed that the effects of OC use on the MRT could be predicted based on the estrogenic strength of the contraceptives used. Estrogenic potency, not androgenic or anti-androgenic effects of the OC pill, may underlie the effects of OC usage on spatial cognition.
The risk of adverse cardiovascular events peaks in the morning (≈9:00 AM) with a secondary peak in the evening (≈8:00 PM) and a trough at night. This pattern is generally believed to be caused by the ...day/night distribution of behavioral triggers, but it is unknown whether the endogenous circadian system contributes to these daily fluctuations. Thus, we tested the hypotheses that the circadian system modulates autonomic, hemodynamic, and hemostatic risk markers at rest, and that behavioral stressors have different effects when they occur at different internal circadian phases. Twelve healthy adults were each studied in a 240-h forced desynchrony protocol in dim light while standardized rest and exercise periods were uniformly distributed across the circadian cycle. At rest, there were large circadian variations in plasma cortisol (peak-to-trough ≈85% of mean, peaking at a circadian phase corresponding to ≈9:00 AM) and in circulating catecholamines (epinephrine, ≈70%; norepinephrine, ≈35%, peaking during the biological day). At ≈8:00 PM, there was a circadian peak in blood pressure and a trough in cardiac vagal modulation. Sympathetic variables were consistently lowest and vagal markers highest during the biological night. We detected no simple circadian effect on hemostasis, although platelet aggregability had two peaks: at ≈noon and ≈11:00 PM. There was circadian modulation of the cardiovascular reactivity to exercise, with greatest vagal withdrawal at ≈9:00 AM and peaks in catecholamine reactivity at ≈9:00 AM and ≈9:00 PM. Thus, the circadian system modulates numerous cardiovascular risk markers at rest as well as their reactivity to exercise, with resultant profiles that could potentially contribute to the day/night pattern of adverse cardiovascular events.
Changes in soil organic carbon (SOC) storage have the potential to affect global climate; hence identifying environments with a high capacity to gain or lose SOC is of broad interest. Many cross‐site ...studies have found that SOC‐poor soils tend to gain or retain carbon more readily than SOC‐rich soils. While this pattern may partly reflect reality, here we argue that it can also be created by a pair of statistical artifacts. First, soils that appear SOC‐poor purely due to random variation will tend to yield more moderate SOC estimates upon resampling and hence will appear to accrue or retain more SOC than SOC‐rich soils. This phenomenon is an example of regression to the mean. Second, normalized metrics of SOC change—such as relative rates and response ratios—will by definition show larger changes in SOC at lower initial SOC levels, even when the absolute change in SOC does not depend on initial SOC. These two artifacts create an exaggerated impression that initial SOC stocks are a major control on SOC dynamics. To address this problem, we recommend applying statistical corrections to eliminate the effect of regression to the mean, and avoiding normalized metrics when testing relationships between SOC change and initial SOC. Careful consideration of these issues in future cross‐site studies will support clearer scientific inference that can better inform environmental management.
Changes in soil organic carbon (SOC) storage have the potential to affect global climate. Many studies have found that SOC‐poor soils tend to gain or retain carbon more readily than SOC‐rich soils, which implies that SOC‐poor soils should be ideal targets for carbon sequestration. While this pattern may partly reflect reality, its importance can also be exaggerated by several common statistical artifacts, such as spurious correlations caused by regression to the mean. To eliminate these artifacts, we recommend applying statistical corrections and avoiding specific data analysis approaches. Careful consideration of these issues will lead to more effective management of SOC.
Inflammation and oxidative stress play major roles in healthy and pathological pregnancy. Environmental exposure to chemical pollutants may adversely affect maternal and fetal health in pregnancy by ...dysregulating these critical underlying processes of inflammation and oxidative stress. Oxylipins are bioactive lipids that play a major role in regulating inflammation and increasing lines of evidence point towards an importance in pregnancy. The biosynthetic production of oxylipins requires oxygenation of polyunsaturated fatty acids, which can occur through several well-characterized enzymatic and nonenzymatic pathways. This review describes the state of the science of epidemiologic evidence on oxylipin production in pregnancy and its association with 1) key pregnancy outcomes and 2) environmental exposures. We searched PubMed for studies of pregnancy that measured one or more oxylipin analytes during pregnancy or delivery. We evaluated oxylipin associations with three categories of adverse pregnancy outcomes, including preeclampsia, preterm birth, and fetal growth restriction, along with several categories of environmental pollutants. The majority of studies evaluated one to two oxylipins, most of which focused on oxylipins produced from nonenzymatic processes of oxidative stress. However, an increasing number of recent studies have leveraged technological advancements to profile a large number of oxylipins produced from distinct biosynthetic pathways. Although the literature indicated robust evidence that oxylipins produced via nonenzymatic pathways are associated with pregnancy outcomes and environmental exposures, evidence for enzymatically produced oxylipins showed that associations may differ between biosynthetic pathways. Along with summarizing this evidence, we review promising therapeutic options to regulate oxylipin production and provide a set of recommendations for future epidemiologic studies in these research areas. Further evidence is needed to improve our understanding of how oxylipins may act as key biological mediators for the adverse effects of environmental pollutants on pregnancy outcomes.
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