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Abstract We investigated the feasibility of using a dopamine transporter (DaT) tracer ligand ([123I]FP-CIT) along with novel multi-pinhole brain collimators for dynamic brain single photon emission computed tomography (SPECT) in suspected Parkinson's disease patients. Thirteen patients underwent dynamic tracer acquisitions before standard imaging. Uptake values were corrected for partial volume effects. Specific binding ratio (SBRcalc) was calculated, reflecting binding potential relative to non-displaceable binding (BPND) in the cortex. Additional pharmacokinetic parameters (BPND, R1, k2) were estimated using the simplified reference tissue model, revealing differences between Kahraman low-score (LS) and high-score (HS) groups. Results showed increasing striatal tracer uptake until 100 min post-injection, with consistent values afterward. Uptake and SBRcalc ratios matched visual assessment. LS patients had lower putamen than caudate nucleus tracer uptake, decreased BPND values, while R1 and k2 values were comparable to HS patients. In conclusion, dynamic multi-pinhole SPECT using DaT tracer with the extraction of pharmacokinetic parameters is feasible and could help enable early differentiation of reduced and normal DaT values.

Nitrous oxide (N2O) emissions from organic waste and animal slurry contribute to climate change and endanger our ecosystems. For the development of efficient mitigation technologies, in-depth knowledge of emission processes is needed. This can be obtained by non-destructive, temporal measurements of in-situ soil profiles and the transformation of ammonium (NH4+) during events of emissions. Planar optode imaging is a non-destructive measuring method that can be used to visualize spatiotemporal changes of ammonia (NH3) and pH in soil systems. In this study, soil amended with dairy processing sludge (DPS) was incubated in static chambers for 23 days, and GHG emissions, NH3 concentrations and pH in the soil were measured simultaneously over time. The aim was to investigate the potential of applying different planar optodes to provide information that gives insight into processes of N2O emissions. The DPS was applied to the soil as a surface layer (SL), with untreated soil as a control (CK). We were able to measure N2O emissions while monitoring spatiotemporal changes of soil pH and NH3 concentrations. The visualized microscale heterogeneity of the soil contributed to a better understanding of N2O emission processes. While technical challenges (e.g., humidity sensitivity of the NH3 optode and airtightness of the chambers) still need to be overcome, the method is a promising non-destructive method to study soil processes after application of different types of soil amendments.

Abstract Invasive species are the second most important reason for species extinction since 1500 ad. In addition, these invasive species can cause vast economic loss. In marine ecoregions, alien species introductions are increasing, and those that become invasive have caused profound changes in many marine ecoregions. We compiled a database consisting of information about where species are alien, where they are not, and which species are listed as threatened by invasive species. In addition, we developed an interactive Webapp for visualizing and analyzing the results. We used the Ocean Biogeographic Information System (OBIS) for identifying the presence of a species in a marine ecoregion. Information from the World Register of Marine Species (WoRMS), the Global Invasive Species Database (GISD), and the Nature Conservancy database on marine invasive species (NatCon) was used to identify the names and locations of marine alien species. Information from the International Union for Conservation of Nature (IUCN) Red List revealed which species are considered to be threatened by invasive species. Our database lists 112,399 marine species, of which 966 are alien species and 1655 are listed as threatened by invasive species by the IUCN. These are distributed throughout 225 marine ecoregions (97% of marine ecoregions). Our results confirm previous studies about the prevalence of alien and invasive species and provide an up‐to‐date status about known and recorded species and their distribution. This information can be used as a fundament for developing impact assessment models and identifying management strategies to combat marine invasive species.

Abstract The corticofugal tracts (CFT) are key agents of upper limb motor function. Although the tracts form high-intensity regions relative to surrounding tissue in T2-weighted magnetic resonance images (T2WI), the precise relations of signal intensities of the left and right CFT regions to hand function are unknown. Here, we tested the hypothesis that the different signal intensities between the left and right CFT signify clinically important differences of hand motor function. Eleven right-handed and eleven left-handed healthy volunteers participated in the study. Based on horizontal T2WI estimates, we confirmed the relationship between the signal intensity ratios of the peak values of each CFT in the posterior limbs of the internal capsules (right CFT vs. left CFT). The ratios included the asymmetry indices of the hand motor functions, including grip and pinch strength, as well as the target test (TT) that expressed the speed and accuracy of hitting a target ([right-hand score − left-hand score]/[right-hand score + left-hand score]), using simple linear regression. The signal intensity ratios of each CFT structure maintained significant linear relations with the asymmetry index of the speed (R2 = 0.493, P = 0.0003) and accuracy (R2 = 0.348, P = 0.004) of the TT. We found no significant association between left and right CFT structures for grip or pinch strengths. The findings are consistent with the hypothesis that the different signal intensities of the left and right CFT images captured by T2WI serve as biological markers that reflect the dominance of manual dexterity.

Mobiletnografi er en ny evalueringsmetode, som har vundet indpas de seneste årtier. Metoden benytter teknologiske devices som fx mobiltelefoner til at indfange og undersøge sociale fænomener på tværs af tid og rum i ikke afgrænsede kontekster. Mobiletnografi muliggør dataindsamling in situ og giver adgang til en anden type kvalitativt data end interviews og observationer. På trods af metodens stadig større udbredelse er der sparsom viden om brugen af mobiletnografi. I denne artikel vil vi drøfte metodens anvendelighed på det sociale område med afsæt i vores erfaringer fra en evaluering af et uddannelsestilbud til psykisk sårbare unge. Nøgleord: Mobiletnografi, psykisk sårbare unge, evalueringsmetoder, digitale data

BackgroundThe autonomic nervous system (ANS) maintains glucose homeostasis. While higher than normal glucose levels stimulate the ANS toward reduction, previous findings suggest an association between sensitivity to, or pain from, pressure at the chest bone (pressure or pain sensitivity, PPS) and activity of the ANS. A recent randomized controlled trial (RCT) of type 2 diabetes (T2DM) suggested that addition of an experimental, non-pharmacological intervention more effectively than conventional treatment lowered the levels of both PPS and HbA1c.Materials and analysesWe tested the null hypothesis that conventional treatment (n = 60) would reveal no association between baseline HbA1c and normalization of HbA1c in 6 months, related to change of PPS. We compared the changes of HbA1c in PPS reverters who experienced a minimum reduction of 15 units of PPS and in PPS non-reverters who experienced no reduction. Depending on the result, we tested the association in a second group of participants with addition of the experimental program (n = 52).ResultsIn the conventional group, PPS reverters experienced normalization of HbA1c that corrected the basal increase, thus disproving the null hypothesis. With the addition of the experimental program, PPS reverters experienced similar reduction. The reduction of HbA1c among reverters averaged 0.62 mmol/mol per mmol/mol increase of baseline HbA1c (P < 0.0001 compared to non-reverters). For baseline HbA1c ≥ 64 mmol/mol, reverters averaged 22% reduction of HbA1c (P < 0.01).ConclusionIn consecutive analyses of two different populations of individuals with T2DM, we demonstrated that the higher the baseline HbA1c, the greater the reduction of HbA1c but only in individuals with a concomitant reduction of sensitivity to PPS, suggesting a homeostatic effect of the autonomic nervous system on glucose metabolism. As such, ANS function, measured as PPS, is an objective measure of HbA1c homeostasis. This observation may be of great clinical importance.

Introduction: Increased theta and delta power and decreased alpha and beta power, measured with quantitative electroencephalography (EEG), have been demonstrated to have utility for predicting the development of dementia in patients with Parkinson’s disease (PD). Noradrenaline modulates cortical activity and optimizes cognitive processes. We claim that the loss of noradrenaline may explain cognitive impairment and the pathological slowing of EEG waves. Here, we test the relationship between the number of noradrenergic α2 adrenoceptors and changes in the spectral EEG ratio in patients with PD. Methods: We included nineteen patients with PD and thirteen healthy control (HC) subjects in the study. We used positron emission tomography (PET) with [11C]yohimbine to quantify α2 adrenoceptor density. We used EEG power in the delta (δ, 1.5–3.9 Hz), theta (θ, 4–7.9 Hz), alpha (α, 8–12.9 Hz) and beta (β, 13–30 Hz) bands in regression analyses to test the relationships between α2 adrenoceptor density and EEG band power. Results: PD patients had higher power in the theta and delta bands compared to the HC volunteers. Patients’ theta band power was inversely correlated with α2 adrenoceptor density in the frontal cortex. In the HC subjects, age was correlated with, and occipital background rhythm frequency (BRF) was inversely correlated with, α2 adrenoceptor density in the frontal cortex, while occipital BRF was inversely correlated with α2 adrenoceptor density in the thalamus. Conclusions: The findings support the claim that the loss or dysfunction of noradrenergic neurotransmission may relate to the parallel processes of cognitive decline and EEG slowing.

Long-term alteration of dopaminergic neurotransmission is known to modulate the D2/D3 receptor expression in the brain. The modulation can occur as a response to pathological processes or pharmacological intervention. The receptor density can be monitored by in vivo positron emission tomography (PET) of [11C] raclopride. To obtain accurate measurements of receptor-ligand interaction, it is essential to estimate binding parameters at true (if transient) equilibrium of bound and unbound ligand quantities. We designed this study as a comparison of two quantitative approaches to transient equilibrium, the TRansient EquilibriuM BoLus Estimation (TREMBLE) method and the Transient Equilibrium Model (TEM) method, to determine binding parameters at transient equilibrium with bolus injection of the radioligand. The data demonstrates that TREMBLE unlike TEM identified the time at which equilibrium existed. TREMBLE revealed that equilibrium prevailed at one or more times after bolus injection and identified differences of receptor density among regions such as putamen and caudate nucleus. We demonstrated that TREMBLE is a quantitative approach suitable for the study of pathophysiological conditions of certain types of neurotransmission the brain. [ABSTRACT FROM AUTHOR]

Because the human brain consumes a disproportionate fraction of the resting body's energy, positron emission tomography (PET) measurements of absolute glucose metabolism (CMRglc) can serve as disease biomarkers. Global mean normalization (GMN) of PET data reveals disease-based differences from healthy individuals as fractional changes across regions relative to a global mean. To assess the impact of GMN applied to metabolic data, we compared CMRglc with and without GMN in healthy awake volunteers with eyes closed (i.e., control) against specific physiological/clinical states, including healthy/awake with eyes open, healthy/awake but congenitally blind, healthy/sedated with anesthetics, and patients with disorders of consciousness. Without GMN, global CMRglc alterations compared to control were detected in all conditions except in congenitally blind where regional CMRglc variations were detected in the visual cortex. However, GMN introduced regional and bidirectional CMRglc changes at smaller fractions of the quantitative delocalized changes. While global information was lost with GMN, the quantitative approach (i.e., a validated method for quantitative baseline metabolic activity without GMN) not only preserved global CMRglc alterations induced by opening eyes, sedation, and varying consciousness but also detected regional CMRglc variations in the congenitally blind. These results caution the use of GMN upon PET-measured CMRglc data in health and disease.

Long-term alteration of dopaminergic neurotransmission is known to modulate the D2/D3 receptor expression in the brain. The modulation can occur as a response to pathological processes or pharmacological intervention. The receptor density can be monitored by in vivo positron emission tomography (PET) of [C11] raclopride. To obtain accurate measurements of receptor-ligand interaction, it is essential to estimate binding parameters at true (if transient) equilibrium of bound and unbound ligand quantities. We designed this study as a comparison of two quantitative approaches to transient equilibrium, the TRansient EquilibriuM BoLus Estimation (TREMBLE) method and the Transient Equilibrium Model (TEM) method, to determine binding parameters at transient equilibrium with bolus injection of the radioligand. The data demonstrates that TREMBLE unlike TEM identified the time at which equilibrium existed. TREMBLE revealed that equilibrium prevailed at one or more times after bolus injection and identified differences of receptor density among regions such as putamen and caudate nucleus. We demonstrated that TREMBLE is a quantitative approach suitable for the study of pathophysiological conditions of certain types of neurotransmission the brain.

Decryption of brain images is the basis for the necessary translation of the findings from imaging to information required to meet the demands of clinical intervention. Tools of brain imaging, therefore, must satisfy the conditions dictated by the needs for interpretation in terms of diagnosis and prognosis. In addition, the applications must serve as fundamental research tools that enable the understanding of new therapeutic drugs, including compounds as diverse as antipsychotics, antidepressants, anxiolytics, and drugs serving the relief of symptoms from neurochemical disorders as unrelated as multiple sclerosis, stroke, and dementia. Here we review and explain the kinetics of methods that enable researchers to describe the brain’s work and functions. We focus on methods invented by neurokineticists and expanded upon by practitioners during decades of experimental work and on the methods that are particularly useful to predict possible future approaches to the treatment of neurochemical disorders. We provide an overall description of the basic elements of kinetics and the underlying quantification methods, as well as the mathematics of modeling the recorded brain dynamics embedded in the images we obtain in vivo. The complex presentation to follow is necessary to justify the contribution of modeling to the development of methods and to support the specifications dictated by the proposed use in clinical settings. The quantification and kinetic modeling processes are equally essential to image reconstruction and labeling of brain regions of structural or functional interest. The procedures presented here are essential tools of scientific approaches to all conventional and novel forms of brain imaging. The foundations of the kinetic and quantitative methods are keys to the satisfaction of clinicians that actively engage in treating the neurochemical disorders of mammalian brains in the fields of neurology, neurosurgery, and neuropsychiatry.

Background: As lifetime expectancy in Greenland is steadily increasing, so is the proportion of elderly Greenlanders. Old age is associated with polypharmacy, and in this study, we aim to describe the prevalence and characteristics of polypharmacy among the care home residents in Greenland. Methods: Eight care homes in Greenland were visited between 2010 and 2016. Questionnaires including information on prescribed medication and comorbidities were collected and analyzed. Drugs were categorized according to Anatomical Therapeutic Chemical (ATC) category, and potential drug–drug interactions (pDDIs) were assessed using the Danish Interaction Database. Polypharmacy was defined as five or more prescribed drugs. Results: All 244 eligible residents were included in the study. The median number of prescribed drugs per resident was six, and women were prescribed more drugs than men (median six versus five). More than 60% of all residents fulfilled the criteria for polypharmacy. The residents in the polypharmacy group had a higher body mass index (26.9 versus 24.3) and more chronic diseases (median two versus one), and more often pulmonary (14% versus 1%) or endocrine disease (22% versus 2%) than in the non-polypharmacy group. The most prescribed drugs belonged to ATC category N (nervous system, 78% of the residents). Finally, pDDIs were found among 61% of the residents and were more common in the capital (77%), which also had the highest proportion of residents with polypharmacy (77%). Conclusion: This is the first study to describe the patterns of polypharmacy and pDDIs among the elderly in care homes in Greenland. Our findings indicate that polypharmacy is as common in Greenland as elsewhere in the Western world, but there are local differences in the prevalence. Plain Language Summary Polypharmacy among the elderly in care homes in Greenland The lifetime expectancy of the Greenlandic population is increasing, and so is the number of elderly Greenlanders. Previous studies have shown that the elderly have a higher risk of being treated with five drugs or more which is called polypharmacy. Polypharmacy can cause unwanted interactions and side effects. In this study, we examine the characteristics of the residents in Greenlandic care homes belonging to this group. Using questionnaires, we gathered information from 244 residents from care homes in eight different towns and settlements in Greenland. Data included types of medication prescribed to the resident, age, gender, cause of stay, and medical history, which allowed us to compare the results between genders and towns. We found that among 244 residents, more than half of all residents were prescribed five or more different drugs, and women were generally prescribed more drugs than men. Those prescribed five or more drugs had a higher body mass index and more diseases than those prescribed fewer drugs. We also found that certain types of medication, mainly painkillers, were the most prescribed. Finally, residents in the care home in Greenland’s capital Nuuk were more often prescribed five or more drugs than elsewhere in Greenland, indicating local differences in Greenland. Our results give an essential insight into the health and medication of the most fragile elderly in Greenland. Polypharmacy seems to be as common here as elsewhere in the Western world and is a point of focus.

In recent years, the field of neuroimaging dramatically moved forward by means of the expeditious development of specific radioligands of novel targets. Among these targets, the synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein of synaptic vesicles, present in all synaptic terminals, irrespective of neurotransmitter content. It is involved in key functions of neurons, focused on the regulation of neurotransmitter release. The ubiquitous expression in gray matter regions of the brain is the basis of its candidacy as a marker of synaptic density. Following the development of molecules derived from the structure of the anti-epileptic drug levetiracetam, which selectively binds to SV2A, several radiolabeled markers have been synthetized to allow the study of SV2A distribution with positron emission tomography (PET). These radioligands permit the evaluation of in vivo changes of SV2A distribution held to be a potential measure of synaptic density in physiological and pathological conditions. The use of SV2A as a biomarker of synaptic density raises important questions. Despite numerous studies over the last decades, the biological function and the expressional properties of SV2A remain poorly understood. Some functions of SV2A were claimed, but have not been fully elucidated. While the expression of SV2A is ubiquitous, stronger associations between SV2A and Υ amino butyric acid (GABA)-ergic rather than glutamatergic synapses were observed in some brain structures. A further issue is the unclear interaction between SV2A and its tracers, which reflects a need to clarify what really is detected with neuroimaging tools. Here, we summarize the current knowledge of the SV2A protein and we discuss uncertain aspects of SV2A biology and physiology. As SV2A expression is ubiquitous, but likely more strongly related to a certain type of neurotransmission in particular circumstances, a more extensive knowledge of the protein would greatly facilitate the analysis and interpretation of neuroimaging results by allowing the evaluation not only of an increase or decrease of the protein level, but also of the type of neurotransmission involved.

Three genotypes of wheat grown at two CO2 concentrations were used in a drought experiment, where water was withheld from the pots at anthesis until stomatal conductance (gs) dropped below 10% of the control and photosynthesis (A) approached zero. The genotypes had different leaf area (Gladius < LM19 < LM62) and while photosynthesis and shoot growth were boosted by elevated CO2, the water use and drying rate were more determined by canopy size than by stomatal density and conductance. The genotypes responded differently regarding number of fertile tillers, seeds per spike and 1000 kernel weight and, surprisingly, the largest genotype (LM62) with high water use showed the lowest relative decrease in grain yield. The maximum photochemical efficiency of photosystem II (Fv/Fm) was only affected on the last day of the drought when the stomata were almost closed although some variation in A was still seen between the genotypes. A close correlation was found between Fv/Fm and % loss of grain yield. It indicates that the precise final physiological stress level measured by Fv/Fm at anthesis/early kernel filling could effectively predict percentage final yield loss, and LM62 was slightly less stressed than the other genotypes, due to only a small discrepancy in finalising the drying period. Therefore, Fv/Fm can be used as a proxy for estimating the yield performance of wheat after severe drought at anthesis.

We investigated the feasibility of using a dopamine transporter (DaT) tracer ligand ([123I]FP-CIT) along with novel multi-pinhole brain collimators for dynamic brain single photon emission computed tomography (SPECT) in suspected Parkinson's disease patients. Thirteen patients underwent dynamic tracer acquisitions before standard imaging. Uptake values were corrected for partial volume effects. Specific binding ratio (SBRcalc) was calculated, reflecting binding potential relative to non-displaceable binding (BPND) in the cortex. Additional pharmacokinetic parameters (BPND, R1, k2) were estimated using the simplified reference tissue model, revealing differences between Kahraman low-score (LS) and high-score (HS) groups. Results showed increasing striatal tracer uptake until 100 min post-injection, with consistent values afterward. Uptake and SBRcalc ratios matched visual assessment. LS patients had lower putamen than caudate nucleus tracer uptake, decreased BPND values, while R1 and k2 values were comparable to HS patients. In conclusion, dynamic multi-pinhole SPECT using DaT tracer with the extraction of pharmacokinetic parameters is feasible and could help enable early differentiation of reduced and normal DaT values. [ABSTRACT FROM AUTHOR]

BackgroundAutonomic nervous system dysfunction (ANSD) is known to affect glucose metabolism in the mammalian body. Tradition holds that glucose homeostasis is regulated by the peripheral nervous system, and contemporary therapeutic intervention reflects this convention.ObjectivesThe present study tested the role of cerebral regulation of ANSD as consequence of novel understanding of glucose metabolism and treatment target in type 2 diabetes (T2D), suggested by the claim that the pressure pain sensitivity (PPS) of the chest bone periosteum may be a measure of cerebral ANSD.DesignIn a randomized controlled trial of 144 patients with T2D, we tested the claim that 6 months of this treatment would reduce PPS and improve peripheral glucose metabolism.ResultsIn the active treatment group, mean glycated hemoglobin A1c (HbA1c) declined from 53.8 to 50.5 mmol/mol (intragroup p = 0.001), compared with the change from 53.8 to 53.4 mmol/mol in the control group, with the same level of diabetes treatment but not receiving the active treatment (between group p = 0.036). Mean PPS declined from 76.6 to 56.1 units (p < 0.001) in the active treatment group and from 77.5 to 72.8 units (p = 0.02; between group p < 0.001) in the control group. Changes of PPS and HbA1c were correlated (r = 0.37; p < 0.001).ConclusionWe conclude that the proposed approach to treatment of T2D is a potential supplement to conventional therapy.Clinical Trial Registration:www.clinicaltrials.gov (NCT 03576430).

Introduction: Increased theta and delta power and decreased alpha and beta power, measured with quantitative electroencephalography (EEG), have been demonstrated to have utility for predicting the development of dementia in patients with Parkinson's disease (PD). Noradrenaline modulates cortical activity and optimizes cognitive processes. We claim that the loss of noradrenaline may explain cognitive impairment and the pathological slowing of EEG waves. Here, we test the relationship between the number of noradrenergic α2 adrenoceptors and changes in the spectral EEG ratio in patients with PD. Methods: We included nineteen patients with PD and thirteen healthy control (HC) subjects in the study. We used positron emission tomography (PET) with [11C]yohimbine to quantify α2 adrenoceptor density. We used EEG power in the delta (δ, 1.5–3.9 Hz), theta (θ, 4–7.9 Hz), alpha (α, 8–12.9 Hz) and beta (β, 13–30 Hz) bands in regression analyses to test the relationships between α2 adrenoceptor density and EEG band power. Results: PD patients had higher power in the theta and delta bands compared to the HC volunteers. Patients' theta band power was inversely correlated with α2 adrenoceptor density in the frontal cortex. In the HC subjects, age was correlated with, and occipital background rhythm frequency (BRF) was inversely correlated with, α2 adrenoceptor density in the frontal cortex, while occipital BRF was inversely correlated with α2 adrenoceptor density in the thalamus. Conclusions: The findings support the claim that the loss or dysfunction of noradrenergic neurotransmission may relate to the parallel processes of cognitive decline and EEG slowing. [ABSTRACT FROM AUTHOR]