590 research outputs found
Electrical system/environment interactions on the planet Mars
The Martian environment is a diverse environment with which systems will interact in numerous ways. Preliminary thoughts on electrical system/environment interactions which might be of interest to system designers at all stages of system design are presented. These interactions are primarily related to electrical charging, contamination, and Martian surface sand and dust
17β-Estradiol Potentiates the Reinstatement of Cocaine Seeking in Female Rats: Role of the Prelimbic Prefrontal Cortex and Cannabinoid Type-1 Receptors
Clinical observations imply that female cocaine addicts experience enhanced relapse vulnerability compared with males, an effect tied to elevated estrogen phases of the ovarian hormone cycle. Although estrogens can enhance drug-seeking behavior, they do not directly induce reinstatement on their own. To model this phenomenon, we tested whether an estrogen could augment drug-seeking behavior in response to an ordinarily subthreshold reinstatement trigger. Following cocaine self-administration and extinction, female rats were ovariectomized to isolate estrogen effects on reinstatement. Although neither peak proestrus levels of the primary estrogen 17β-estradiol (E2; 10 μg/kg, i.p., 1-h pretreatment) nor a subthreshold cocaine dose (1.25 mg/kg, i.p.) alone were sufficient to reinstate drug-seeking behavior, pretreatment with E2 potentiated reinstatement to the ordinarily subthreshold cocaine dose. Furthermore, E2 microinfusions revealed that E2 (5 μg/0.3 μl, 15-min pretreatment) acts directly within the prelimbic prefrontal cortex (PrL-PFC) to potentiate reinstatement. As E2 has been implicated in endocannabinoid mobilization, which can disinhibit PrL-PFC projection neurons, we investigated whether cannabinoid type-1 receptor (CB1R) activation is necessary for E2 to potentiate reinstatement. The CB1R antagonist AM251 (1 or 3 mg/kg, i.p., 30-min pretreatment) administered prior to E2 and cocaine suppressed reinstatement in a dose-dependent manner. Finally, PrL-PFC AM251 microinfusions (300 ng/side, 15-min pretreatment) also suppressed E2-potentiated reinstatement. Together, these results suggest that E2 can augment reactivity to an ordinarily subthreshold relapse trigger in a PrL-PFC CB1R activation-dependent manner
Computed Tomography Shows High Fracture Prevalence Among Physically Active Forager-Horticulturalists With High Fertility
Modern humans have more fragile skeletons than other hominins, which may result from physical inactivity. Here, we test whether reproductive effort also compromises bone strength, by measuring using computed tomography thoracic vertebral bone mineral density (BMD) and fracture prevalence among physically active Tsimane forager-horticulturalists. Earlier onset of reproduction and shorter interbirth intervals are associated with reduced BMD for women. Tsimane BMD is lower versus Americans, but only for women, contrary to simple predictions relying on inactivity to explain skeletal fragility. Minimal BMD differences exist between Tsimane and American men, suggesting that systemic factors other than fertility (e.g. diet) do not easily explain Tsimane women’s lower BMD. Tsimane fracture prevalence is also higher versus Americans. Lower BMD increases Tsimane fracture risk, but only for women, suggesting a role of weak bone in women’s fracture etiology. Our results highlight the role of sex-specific mechanisms underlying skeletal fragility that operate long before menopause
Age-Independent Increases in Male Salivary Testosterone During Horticultural Activity Among Tsimane Forager-Farmers
Testosterone plays an important role in mediating male reproductive trade-offs in many vertebrate species, augmenting muscle and influencing behavior necessary for male-male competition and mating-effort. Among humans, testosterone may also play a key role in facilitating male provisioning of offspring as muscular and neuromuscular performance are deeply influenced by acute changes in testosterone. This study examines acute changes in salivary testosterone among 63 Tsimane men ranging in age from 16–80 (mean 38.2) years during one-hour bouts of treechopping while clearing horticultural plots. The Tsimane forager-horticulturalists living in the Bolivian Amazon experience high energy expenditure associated with food production, have high levels of parasites and pathogens, and display significantly lower baseline salivary testosterone than age-matched US males. Mixed-effects models controlling for BMI and time of specimen collection reveal increased salivary testosterone (p\u3c0.001) equivalent to a 48.6% rise, after one hour of tree chopping. Age had no effect on baseline (p=0.656) or change in testosterone (p=0.530); self-reported illness did not modify testosterone change (p=0.488). A comparison of these results to the relative change in testosterone during a competitive soccer tournament in the same population reveals larger relative changes in testosterone following resource production (tree chopping), compared to competition (soccer). These findings highlight the importance of moving beyond a unidimensional focus on changes in testosterone and male-male aggression to investigate the importance of testosterone-behavior interactions across additional male fitness-related activities. Acutely increased testosterone during muscularly intensive horticultural food production may facilitate male productivity and provisioning
Intracranial stereotactic radiation therapy with a jawless ring gantry linear accelerator equipped with new dual layer multileaf collimator
Purpose: To test the feasibility of a simplified, robust, workflow for intracranial stereotactic radiation therapy (SRT) using a ring gantry linear accelerator (RGLA) equipped with a dual-layer stacked, staggered, and interdigitating multileaf collimator.
Materials and Methods: Twenty recent clinical SRT cases treated using a radiosurgery c-arm linear accelerator were anonymized. From these data sets, a new planning workflow was developed and used to replan these cases, which then were compared to their clinical counterparts. Population-based dose-volume histograms were analyzed for target coverage and sparing of healthy brain. All plans underwent plan review and quality assurance and were delivered on an end-to-end verification phantom using image guidance to simulate treatment.
Results: The RGLA plans were able to meet departmental standards for target coverage and organ-at-risk sparing and showed plan quality similar to the clinical plans. RGLA plans showed increases in the 50% isodose in the axial plane but decreases in the sagittal and coronal planes. There were no statistically significant differences in the homogeneity index or number of monitor units between the 2 systems. There were statistically significant increases in conformity and gradient indices, with median values of 1.09 versus 1.11 and 2.82 versus 3.13, respectively, for the c-arm versus RGLA plans. These differences were not believed to be clinically significant because they met clinical goals. The population-based dose-volume histograms showed target coverage and organ-at-risk sparing similar to that of the clinical plans. All plans were able to meet the departmental quality assurance requirements and were delivered under image guidance on an end-to-end phantom with measurements agreeing within 3% of the expected value. RGLA plans showed a median reduction in delivery time of ≈50%.
Conclusions: This work describes a simplified and efficient workflow that could reduce treatment times and expand access to SRT to centers using an RGLA
Endocannabinoid regulation of amyloid-induced neuroinflammation
The modulation of endocannabinoid (EC) levels and the activation of cannabinoid receptors are seen as promising therapeutic strategies in a variety of diseases, including Alzheimer’s disease (AD). We aimed to evaluate the effect of the pharmacological and genetic inhibiton of anandamide (AEA)-degrading enzyme in a mouse model of AD (5xFAD). Pharmacological inhibition of the fatty acid amide hydrolase (FAAH) had little impact on the expression of key enzymes and cytokines as well as on the cognitive impairment and plaque deposition and gliosis in 5xFAD mice. CB1 blockade exacerbated inflammation in this transgenic mouse model of AD. The genetic inactivation of FAAH led to increases in the expression of inflammatory cytokines. At the same time, FAAH-null 5xFAD mice exhibited a behavioral improvement in spatial memory that was independent of the level of anxiety and was not CB1-mediated. Finally, mice lacking FAAH showed diminished soluble amyloid levels, neuritic plaques and gliosis. These data reinforce the notion of a role for the endocannabinoid system in neuroinflammation and open new perspectives on the relevance of modulating endocannabinoid levels in the inflammed brain.pre-print687 K
Fatty Acid Composition in the Mature Milk of Bolivian Forager-Horticulturalists: Controlled Comparisons With a US Sample
Breast milk fatty acid (FA) composition varies greatly among individual women, including in percentages of the long-chain polyunsaturated FAs (LCPUFA) 20:4n-6 (arachidonic acid, AA) and 22:6n-3 (docosahexaenoic acid, DHA), which are important for infant neurological development. It has been suggested that owing to wide variation in milk LCPUFA and low DHA in Western diets, standards of milk FA composition should be derived from populations consuming traditional diets. We collected breast milk samples from Tsimane women at varying lactational stages (6–82 weeks). The Tsimane are an indigenous, natural fertility, subsistence-level population living in Amazonia Bolivia. Tsimane samples were matched by lactational stage to samples from a US milk bank, and analysed concurrently for FA composition by gas-liquid chromatography. We compared milk FA composition between Tsimane (n = 35) and US (n = 35) mothers, focusing on differences in LCPUFA percentages that may be due to population-typical dietary patterns. Per total FAs, the percentages of AA, DHA, total n-3 and total n-6 LCPUFA were significantly higher among Tsimane mothers. Mean percentages of 18:2n-6 (linoleic acid) and trans FAs were significantly higher among US mothers. Tsimane mothers’ higher milk n-3 and n-6 LCPUFA percentages may be due to their regular consumption of wild game and freshwater fish, as well as comparatively lower intakes of processed foods and oils that may interfere with LCPUFA synthesis
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