Differences in peripheral noradrenergic function among actively drinking and abstinent alcohol-dependent individuals.

We examined whether excessive alcohol consumption was related to changes in plasma levels of noradrenaline (NA) and whether these changes recover following abstinence. We also explored whether there were differences in NA levels between Type I and Type II alcoholics and controls during active drinking and abstinence. Plasma concentrations of NA were determined in (1) 27 Caucasian men with alcohol dependence who were regularly drinking (active drinkers) within 24 hours of hospitalization, (2) 29 Caucasian alcohol-dependent men who were in remission (abstinent for a minimum of three months), and (3) 28 race- and gender-matched healthy controls. NA concentrations were significantly higher in actively drinking alcohol-dependent subjects compared to those in remission and controls. While Type I and Type II alcoholic individuals differed across clinical measures, NA levels were similar in the two subtypes. Both subtypes showed an elevation in NA levels during active drinking compared to controls, but NA levels did not differ between the two subtypes and controls during remission. The findings indicate that chronic exposure to alcohol may lead to disturbances in NA activity that may manifest in early abstinence. However, the changes in NA activity appears to normalize after a longer period of abstinence. Alterations in NA activity do not seem to be specific for Type I or Type II subtypes of alcoholism

Time-Dependent Vascular Effects of Endocannabinoids Mediated by Peroxisome Proliferator-Activated Receptor Gamma (PPARγ)

The aim of the present study was to examine whether endocannabinoids cause PPARγ-mediated vascular actions. Functional vascular studies were carried out in rat aortae. Anandamide and N-arachidonoyl-dopamine (NADA), but not palmitoylethanolamide, caused significant vasorelaxation over time (2 hours). Vasorelaxation to NADA, but not anandamide, was inhibited by CB1 receptor antagonism (AM251, 1 μM), and vasorelaxation to both anandamide and NADA was inhibited by PPARγ antagonism (GW9662, 1 μM). Pharmacological inhibition of de novo protein synthesis, nitric oxide synthase, and super oxide dismutase abolished the responses to anandamide and NADA. Removal of the endothelium partly inhibited the vasorelaxant responses to anandamide and NADA. Inhibition of fatty acid amide hydrolase (URB597, 1 μM) inhibited the vasorelaxant response to NADA, but not anandamide. These data indicate that endocannabinoids cause time-dependent, PPARγ-mediated vasorelaxation. Activation of PPARγ in the vasculature may represent a novel mechanism by which endocannabinoids are involved in vascular regulation

Turbulent dispersal promotes species coexistence

Several recent advances in coexistence theory emphasize the importance of space and dispersal, but focus on average dispersal rates and require spatial heterogeneity, spatio-temporal variability or dispersal-competition tradeoffs to allow coexistence. We analyse a model with stochastic juvenile dispersal (driven by turbulent flow in the coastal ocean) and show that a low-productivity species can coexist with a high-productivity species by having dispersal patterns sufficiently uncorrelated from those of its competitor, even though, on average, dispersal statistics are identical and subsequent demography and competition is spatially homogeneous. This produces a spatial storage effect, with an ephemeral partitioning of a ‘spatial niche’, and is the first demonstration of a physical mechanism for a pure spatiotemporal environmental response. ‘Turbulent coexistence’ is widely applicable to marine species with pelagic larval dispersal and relatively sessile adult life stages (and perhaps some wind-dispersed species) and complements other spatial and temporal storage effects previously documented for such species

Empiric treatment of pulmonary TB in the Xpert era: Correspondence of sputum culture, Xpert MTB/RIF, and clinical diagnoses.

BackgroundClinical tuberculosis diagnosis and empiric treatment have traditionally been common among patients with negative bacteriologic test results. Increasing availability of rapid molecular diagnostic tests, including Xpert MTB/RIF and the new Xpert Ultra cartridge, may alter the role of empiric treatment.MethodsWe prospectively enrolled outpatients age > = 15 who were evaluated for pulmonary tuberculosis at three health facilities in Kampala, Uganda. Using sputum mycobacterial culture, interviews, and clinical record abstraction, we estimated the accuracy of clinical diagnosis relative to Xpert and sputum culture and assessed the contribution of clinical diagnosis to case detection.ResultsOver a period of 9 months, 99 patients were diagnosed with pulmonary tuberculosis and subsequently completed sputum culture; they were matched to 196 patients receiving negative tuberculosis evaluations in the same facilities. Xpert was included in the evaluation of 291 (99%) patients. Compared to culture, Xpert had a sensitivity of 92% (95% confidence interval 83-97%) and specificity of 95% (92-98%). Twenty patients with negative Xpert were clinically diagnosed with tuberculosis and subsequently had their culture status determined; two (10%) were culture-positive. Considering all treated patients regardless of Xpert and culture data completeness, and considering treatment initiations before a positive Xpert (N = 4) to be empiric, 26/101 (26%) tuberculosis treatment courses were started empirically. Compared to sputum smear- or Xpert-positive patients with positive cultures, empirically-treated, Xpert-negative patients with negative cultures had higher prevalence of HIV (67% versus 37%), shorter duration of cough (median 4 versus 8 weeks), and lower inflammatory markers (median CRP 7 versus 101 mg/L).ConclusionJudged against sputum culture in a routine care setting of high HIV prevalence, the accuracy of Xpert was high. Clinical judgment identified a small number of additional culture-positive cases, but with poor specificity. Although clinicians should continue to prescribe tuberculosis treatment for Xpert-negative patients whose clinical presentations strongly suggest pulmonary tuberculosis, they should also carefully consider alternative diagnoses

LunaNet: a Flexible and Extensible Lunar Exploration Communications and Navigation Infrastructure

NASA has set the ambitious goal of establishing a sustainable human presence on the Moon. Diverse commercial and international partners are engaged in this effort to catalyze scientific discovery, lunar resource utilization and economic development on both the Earth and at the Moon. Lunar development will serve as a critical proving ground for deeper exploration into the solar system. Space communications and navigation infrastructure will play an integral part in realizing this goal. This paper provides a high-level description of an extensible and scalable lunar communications and navigation architecture, known as LunaNet. LunaNet is a services network to enable lunar operations. Three LunaNet service types are defined: networking services, position, navigation and timing services, and science utilization services. The LunaNet architecture encompasses a wide variety of topology implementations, including surface and orbiting provider nodes. In this paper several systems engineering considerations within the service architecture are highlighted. Additionally, several alternative LunaNet instantiations are presented. Extensibility of the LunaNet architecture to the solar system internet is discussed

SYNTHETIC BIOLOGY APPLIED IN THE AGRIFOOD SECTOR: SOCIETAL PRIORITIES AND PITFALLS

Synthetic biology offers potential for innovation in the agrifood sector, although concerns have been raised consumer rejection of applications will occur similar to that associated with the introduction of genetically modified foods. Risk-benefit assessment should address socio-economic, as well as health and environmental impacts. Ethical issues may be of particular relevance to the application synthetic biology, and may also resonate with societal concerns. A case-by-case analysis of relevant issues may be needed, and innovation must be driven by societal and consumer preferences as well as technological possibilities. Research into consumer and societal priorities is required early in the innovation trajector

The organization of frequency and binaural cues in the gerbil inferior colliculus: GRAÑA et al.

The inferior colliculus (IC) is the common target of separate pathways that transmit different types of auditory information. Beyond tonotopy, little is known about the organization of response properties within the 3-dimensional layout of the auditory midbrain in most species. Through study of interaural time difference (ITD) processing, the functional properties of neurons can be readily characterized and related to specific pathways. To characterize the representation of ITDs relative to the frequency and hodological organization of the IC, the properties of neurons were recorded and the sites recovered histologically. Subdivisions of the IC were identified based on cytochrome oxidase (CO) histochemistry. The results were plotted within a framework formed by an MRI atlas of the gerbil brain. The central nucleus was composed of two parts, and lateral and dorsal cortical areas were identified. The lateral part of the central nucleus had the highest CO activity in the IC and a high proportion of neurons sensitive to ITDs. The medial portion had lower CO activity and fewer ITD-sensitive neurons. A common tonotopy with a dorsolateral to ventromedial gradient of low to high frequencies spanned the two regions. The distribution of physiological responses was in close agreement with known patterns of ascending inputs. An understanding of the 3-dimensional organization of the IC is needed to specify how the single tonotopic representation in the IC central nucleus leads to the multiple tonotopic representations in core areas of the auditory cortex

Association Between Gabapentin Receipt for Any Indication and Alcohol Use Disorders Identification Test-Consumption Scores Among Clinical Subpopulations With and Without Alcohol Use Disorder.

BACKGROUND: Current medications for alcohol use disorder (AUD) have limited efficacy and utilization. Some clinical trials have shown efficacy for gabapentin among treatment-seeking individuals. The impact of gabapentin on alcohol consumption in a more general sample remains unknown. METHODS: We identified patients prescribed gabapentin for ≥180 consecutive days for any clinical indication other than substance use treatment between 2009 and 2015 in the Veterans Aging Cohort Study. We propensity-score matched each gabapentin-exposed patient with up to 5 unexposed patients. Multivariable difference-in-difference (DiD) linear regression models estimated the differential change in Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores during follow-up between exposed and unexposed patients, by baseline level of alcohol consumption and daily gabapentin dose. Analyses were stratified by AUD history. Clinically meaningful changes were a priori considered a DiD ≥1 point. RESULTS: Among patients with AUD, AUDIT-C scores decreased 0.39 points (95% confidence interval [CI] 0.05, 0.73) more among exposed than unexposed patients (p < 0.03). Potentially clinically meaningful differences were observed among those with AUD and exposed to ≥1,500 mg/d (DiD 0.77, 95% CI 0.15, 1.38, p < 0.02). No statistically significant effects were found among patients with AUD at doses lower than 1,500 mg/d or baseline AUDIT-C ≥4. Among patients without AUD, we found no overall difference in changes in AUDIT-C scores, nor in analyses stratified by baseline level of alcohol consumption. CONCLUSIONS: Patients exposed to doses of gabapentin consistent with those used in clinical trials, particularly those with AUD, experienced a greater decrease in AUDIT-C scores than matched unexposed patients

Resistance Training and Quality of Life Among Younger and Older Adults

Older adults are at risk for sarcopenia, which can lead to reduced physical function, physical activity, and quality of life (QoL). PURPOSE: To determine the effects of aging and sedentary behavior on risk for sarcopenia, the purpose was to compare resistance trained and nonresistance trained younger and older adults on two sarcopenia-related outcomes: QoL and physical activity level (PA). METHODS: Younger (23.8 ± 0.4) and older (68.5 ± 1.2) healthy adults were categorized into 4 groups: young trained (YT: n = 22), young not trained (YNT: n = 16), old trained (OT: n = 17), and old not trained (ONT: n = 21). Resistance trained participants trained ≥ 2X per week, for the past ≥ 6 months. Participants completed a survey to assess health-related QoL, using the Sarcopenia and Quality of Life Questionnaire (SarQoL), and PA, using the Leisure Time Exercise Questionnaire (LTEQ). The SarQoL provides a total QoL score based on 7 dimensions. We were interested in total QoL and the following 3 dimensions: physical and mental health, functionality, and activities of daily living (ADLs). Scores range from 0 (worst health) to 100 (best health). The LTEQ provides a score for PA units, based on vigorous, moderate, and light PA in the past week, with higher scores indicating more PA. ANOVAs were used to determine group differences for each variable, p ≤ 0.05. Data are reported as mean ± SE. RESULTS: Group differences emerged for all variables (p ≤ 0.05). For total QoL, YT (94.5 ± 1.4) was significantly higher than all other groups (YNT: 86.4 ± 1.6, p \u3c 0.001; OT: 87.1 ± 1.6, p = 0.001; ONT: 81.9 ± 1.4, p \u3c 0.001). OT (p = 0.017) and YNT (p = 0.039) were significantly higher than ONT. For physical and mental health, YT (94.2 ± 2.4) was significantly higher than all groups (YNT: 82.2 ± 2.8, p = 0.002; OT: 85.8 ± 2.7, p = 0.022; ONT: 77.9 ± 2.4, p \u3c 0.001). OT was significantly higher than ONT (p = 0.035). For functionality (e.g., balance, climbing stairs), YT (97.5 ± 1.4) again was significantly higher than the other groups (YNT: 92.0 ± 1.6, p = 0.012; OT: 88.9 ± 1.6, p \u3c 0.001; ONT: 85.6 ± 1.4, p \u3c 0.001). YNT was significantly higher than ONT (p= 0.004). For ADLs (e.g., difficulty, fatigue, or pain during physical effort), YT (95.4 ± 1.7) was significantly higher than all groups (YNT: 87.3 ± 1.9, p = 0.002; OT: 87.9 ± 1.9, p = 0.004; ONT: 84.7 ± 1.7, p \u3c 0.001). For all QoL variables, OT did not differ from YNT (p \u3e 0.05). For PA, YT (58.5 ± 6.1 AU) had the same activity level as OT (50.0 ± 6.9 AU, p = 0.356). YT was significantly higher than YNT (31.1 ± 7.3 AU, p = 0.005) and ONT (32.4 ± 6.4 AU, p = 0.004). All other group comparisons were not different (p \u3e 0.05). CONCLUSION: Interestingly, OT was similar to YT on PA and similar to YNT on QoL outcomes. Further, OT was higher than ONT on perceptions of physical and mental health and total QoL. These data suggest that resistance training may be an effective modality to improve or maintain QoL as individuals age