VT Values Research Articles

Monoamine Oxidase B Total Distribution Volume in the Prefrontal Cortex of Major Depressive Disorder

Monoamine oxidase B (MAO-B) is an important, high-density enzyme in the brain that generates oxidative stress by hydrogen peroxide production, alters mitochondrial function, and metabolizes nonserotonergic monoamines. Recent advances in positron emission tomography radioligand development for MAO-B in humans enable highly quantitative measurement of MAO-B distribution volume (MAO-B VT), an index of MAO-B density. To date, this is the first investigation of MAO-B in the brain of major depressive disorder that evaluates regions beyond the raphe and amygdala. To investigate whether MAO-B VT is elevated in the prefrontal cortex in major depressive episodes (MDEs) of major depressive disorder. This case-control study was performed at a tertiary care psychiatric hospital from April 1, 2014, to August 30, 2018. Twenty patients with MDEs without current psychiatric comorbidities and 20 age-matched controls underwent carbon 11-labeled [11C]SL25.1188 positron emission tomography scanning to measure MAO-B VT. All participants were drug and medication free, nonsmoking, and otherwise healthy. The MAO-B VT in the prefrontal cortex (PFC). The second main outcome was to evaluate the association between MAO-B VT in the PFC and duration of major depressive disorder illness. Twenty patients with MDEs (mean [SD] age, 34.2 [13.2] years; 11 women) and 20 healthy controls (mean [SD] age, 33.7 [13.1] years; 10 women) were recruited. Patients with MDEs had significantly greater MAO-B VT in the PFC (mean, 26%; analysis of variance, F1,38 = 19.6, P < .001). In individuals with MDEs, duration of illness covaried positively with MAO-B VT in the PFC (analysis of covariance, F1,18 = 15.2, P = .001), as well as most other cortex regions and the thalamus. Fifty percent (10 of 20) of patients with MDEs had MAO-B VT values in the PFC exceeding those of healthy controls. Greater MAO-B VT is an index of MAO-B overexpression, which may contribute to pathologies of mitochondrial dysfunction, elevated synthesis of neurotoxic products, and increased metabolism of nonserotonergic monoamines. Hence, this study identifies a common pathological marker associated with downstream consequences poorly targeted by the common selective serotonin reuptake inhibitor treatments. It is also recommended that the highly selective MAO-B inhibitor medications that are compatible for use with other antidepressants and have low risk for hypertensive crisis should be developed or repurposed as adjunctive treatment for MDEs.

Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2.

L-type amino acid transporter 1 (LAT1) is strongly expressed on the cell membrane in various types of human cancer cells, while being minimally expressed in normal or inflammatory tissues. Therefore, LAT1-targeting PET tracers have been developed for cancer-specific imaging. The purpose of this study was to study the distribution of two LAT1-targeting PET tracers, L-4-borono-2-18F-fluoro-phenylalanine (18F-FBPA) and L-3-18F-alpha-methyl tyrosine (18F-FAMT), in relation to the tumor blood flow, using rat xenograft models. Rat tumor xenograft models of C6 glioma (n = 4; tumors = 8) and MIA PaCa-2 (pancreatic cancer) (n = 4; tumors = 6) were used. The expressions of LAT1 and CD98hc were evaluated by both immunofluorescence staining and western blot analysis. Dynamic PET was performed after injection of 18F-FAMT or 18F-FBPA (scan duration = 70min) following 15O-water PET (scan duration = 10min). The PET data were subjected to kinetic analyses, and the K1, k2, and total distribution volume (Vt) were calculated using the one-tissue compartment model. The accumulation of the LAT1 tracers was expressed in terms of their Vt. Tumor blood flow (TBF) was represented by the K1 value in 15O-water PET. LAT1/CD98hc expression was confirmed in both xenografts by immunofluorescence staining. Western blot analysis showed higher functional expression of LAT1 in the C6 glioma cells as compared to the MIA PaCa-2 cells (C6 glioma/MIA PaCa-2 relative expression ratio = 1.70). The Vt values of both 18F-FBPA and 18F-FAMT were significantly higher in the C6 glioma xenografts than in the MIA PaCa-2 xenografts (C6 glioma: 2.27 ± 0.35 and 2.03 ± 0.23, respectively; MIA PaCa-2: 1.28 ± 0.26 and 1.35 ± 0.15, respectively). Meanwhile, there was no significant correlation of the Vt value of either 18F-FBPA or 18F-FAMT with the TBF, in either the C6 glioma or the MIA PaCa-2 xenografts. This study revealed that total distribution volumes of the LAT1-targeting PET tracers 18F-FBPA and 18F-FAMT were independent of the tumor blood flow and might reflect the functional expression levels of LAT1 in the C6 glioma and MIA PaCa-2 xenograft models.

Radio Recombination Lines in Orion A at 8 and 13 mm: The Ionization Structure and Effective Temperature of the Star θ1 C Ori, the Electron Temperature of the Ionized Gas and Turbulence

The radio recombination lines (RRLs) of hydrogen, helium (H, He) and carbon (C) have been observed at several positions of the HII region Orion A with the RT-22 radio telescope (Pushchino) at 8 and 13 mm. Information about the ionization structure of the HII region has been obtained. The behavior of y+ = n(He+)/n(H+) over the nebula and model calculations suggest that the effective temperature (Teff) of the star θ1 C Ori is in the range 35 000–37 500 K, corresponding to a spectral type ≈O6.5 V, which is important for the calibration of hot O-B stars. The electron temperatures (Te) of this HII region have been measured by taking into account the departures from local thermodynamic equilibrium (LTE); their distribution over the nebula up to distances of 300 arcsec from the center has been derived. The inferred temperatures are in the range 6600–8400 K, strictly decreasing in the eastward directionwith distance from the center, also tend to drop toward the periphery in the southward and westward directions. The turbulent velocities (Vt) of the ionized gas and their distribution over the nebula have been determined. The values of Vt inferred from H RRLs are in the range 9–13 km s−1.

Quality of life dynamics in patients with ischemic heart disease after percutaneous coronary intervention with stent implantation

Percutaneous coronary intervention (PCI) with stenting in patients with stable ischemic heart disease (IHD) is not always accompanied by a significant improvement of clinical symptoms and quality of life (QOL), because of the presence of affective disorders. The aim of this study was to investigate the dynamics of QOL in patients with stable IHD after PCI and conservative treatment, depending on the presence of symptoms of anxiety and depression. In the group of patients with comorbid symptoms of anxiety-depressive disorders, the initial values of GH, VT, SF, RE, MH according to the SF-36 scale were low during PCI. After PCI, QOL of patients in this group improved, and the studied parameters became comparable to those in the group without affective symptoms. In the group of conservative treatment with concomitant symptoms of anxiety and depression, RP, GH, VT, SF and MH values were initially low. A significant dynamics of QOL in patients of this group was not observed after the conservative treatment. In patients without affective symptoms, there was an improvement in SF and RE after the conservative treatment at the 3 months follow-up.

In vivo evaluation of [11C]TMI, a COX-2 selective PET tracer, in baboons

Overexpression of Cyclooxygenase-2 (COX-2) enzyme is associated with the pathogenesis of inflammation, cancers, stroke, arthritis, and neurological disorders. Because of the involvement of COX-2 in these diseases, quantification of COX-2 expression using Positron Emission Tomography (PET) may be a biological marker for early diagnosis, monitoring of disease progression, and an indicator of effective treatment. At present there is no target-specific or validated PET tracer available for in vivo quantification of COX-2. The objective of this study is to evaluate [11C]TMI, a selective COX-2 inhibitor (Ki ≤ 1 nM) in nonhuman primates using PET imaging. PET imaging in baboons showed that [11C]TMI penetrates the blood brain barrier (BBB) and accumulates in brain in a somewhat heterogeneous pattern. Metabolite analyses indicated that [11C]TMI undergoes no significant metabolism of parent tracer in the plasma for baseline scans, however a relative faster metabolism was found for blocking scan. All the tested quantification approaches provide comparable tracer total distribution volume (VT) estimates in the range of 3.2–7 (mL/cm3). We observed about 25% lower VT values in blocking studies with meloxicam, a nonselective COX-2 inhibitor, compared to baseline [11C]TMI binding. Our findings indicate that [11C]TMI may be a suitable PET tracer for the quantification of COX-2 in vivo. Further experiments are needed to confirm the potential of this tracer in COX-2 overexpressing models for brain diseases.

Gas production and in vitro degradability of sheep diets containing propolis ethanolic extract

SUMMARY This study evaluated the influence of the propolis ethanolic extract (PEE) on gas production and in vitro degradability of sheep diets. Five experimental diets (treatments) were evaluated: without addition of PEE; 6 mL PEE; 12 mL PEE; 24 mL PEE and 36 mL PEE/kg concentrate. The experimental diet consisted of 50% elephant grass (Pennisetum purpureum) and 50% concentrate. There was a quadratic effect (P &lt;0.05) for the volumes of total gas production (Vt), gases produced by the rapid degradation fractions (Vf1), and for in vitro degradability at 120 hours (Deg120), where the lowest values of Vt, Vf1 and Deg120, were found for the inclusion of 9.4 mL PEE/kg concentrate. Gas production by fermentation of the slow degradation fraction (Vf2) presented a mean of 25 mL/g DM (P &lt;0.05). The colonization time of food particles (λ) significantly reduced (P&lt;0.05) with increasing inclusion of PEE. Thus, it can be concluded that the PEE up to the inclusion of 9.4 mL/kg concentrate was efficient in inhibiting in vitro total gas production and from the fractions of rapid degradation by 9.9 and 15.3%, respectively, in addition to promoting a reduction of 5.3% in degradability after 120 h incubation in diets with a concentrate: forage ratio of 50:50. Thus, the inhibition in gas production was proportionally greater than the reduction of degradability.

Quantifying SV2A density and drug occupancy in the human brain using [11C]UCB-J PET imaging and subcortical white matter as reference tissue.

A [11C]UCB-J blocking study was performed in healthy volunteers to validate simplified, non-invasive measures for quantifying presynaptic SV2A expression using subcortical white matter as reference tissue. Ninety minutes dynamic [11C]UCB-J PET scanning with arterial blood sampling was performed in 10 healthy volunteers (8M/2F; age 27.6 ± 10.0yrs), before and after administration of a novel chemical entity with selective affinity for SV2A. The centrum semi-ovale (SO) was validated as reference region by comparing baseline and post treatment distribution volume (VT). Using SO as reference tissue, Binding Potential (BPSO) using a Simplified Reference Tissue Model (SRTM, down to 60min acquisition) and Standardized Uptake Value Ratios (60-90min post injection - SUVRSO,60-90min) were compared with regional distribution volume ratios (DVR). Next, SV2A occupancy values based on SRTM BPSOand SUVRSO,60-90min were compared to occupancy estimates using regional VT values and a Lassen plot. After pretreatment, regional VT values were reduced significantly except for SO. Highly significant correlations were found between DVR, SRTM BPSO and SUVRSO,60-90min. Compared to DVR, baseline SRTM BPSO showed a small bias (≤ 6.1%) with lower precision for shorter acquisition times, while SUVRSO,60-90min showed 3.5% bias with similar precision. Differences between SV2A occupancy values based on SUVRSO,60-90min and occupancy estimates using VT and a Lassen plot were small but significant, while negligible bias was found for SRTM based occupancy estimates (at least 70min acquisition). This [11C]UCB-J blocking study validated SO as a suitable reference region for non-invasive quantification of SV2A availability and drug occupancy in the human brain. Accurate quantification can be achieved by using either SUVRSO,60-90min with a 60-90min PET acquisition or SRTM BPSOwith at least 70min dynamic PET acquisition.

Особливості процесу структуроутворення нанокомпозитів на основі поліетилену за його наповнення вуглецевими нанотрубками

Встановлено закономірності структуроутворення під час кристалізації полімерних нанокомпозитів на основі поліетилену, наповненого вуглецевими нанотрубками. Виявлено ефекти впливу на ці закономірності таких факторів, як масова частка наповнювача, швидкість охолодження і метод отримання композитів. Розгляду підлягали нанокомпозити, отримані методом, що базується на змішуванні компонентів у сухому вигляді і в розплаві полімеру. Виконано зіставлення експериментальних екзотерм кристалізації для досліджуваних композитів за зазначених методів їх отримання. З використанням екзотерм кристалізації і рівняння нуклеації отримано дані про особливості структуроутворення на початковій стадії кристалізації композитів. Встановлено, що на цій стадії наявний площинний і об'ємний механізм структуроутворення за деякого переважання останнього. Виконано аналіз закономірностей структуроутворення на стадії кристалізації в об'ємі композитів у цілому в припущенні наявності двох механізмів кристалоутворення, перший з яких пов'язаний з кристалізацією на флуктуаціях густини полімеру, другий – із кристалізацією, в якій роль її центрів відіграють частинки наповнювача. Показано, що механізми кристалізації на частинках наповнювача істотно залежать від його масової частки і методу отримання композиційних матеріалів.

Noninvasive Relative Quantification of [11C]ABP688 PET Imaging in Mice Versus an Input Function Measured Over an Arteriovenous Shunt

Impairment of the metabotropic glutamate receptor 5 (mGluR5) has been implicated with various neurologic disorders. Although mGluR5 density can be quantified with the PET radiotracer [11C]ABP688, the methods for reproducible quantification of [11C]ABP688 PET imaging in mice have not been thoroughly investigated yet. Thus, this study aimed to assess and validate cerebellum as reference region for simplified reference tissue model (SRTM), investigate the feasibility of a noninvasive cardiac image-derived input function (IDIF) for relative quantification, to validate the use of a PET template instead of an MRI template for spatial normalization, and to determine the reproducibility and within-subject variability of [11C]ABP688 PET imaging in mice. Blocking with the mGluR5 antagonist MPEP resulted in a reduction of [11C]ABP688 binding of 41% in striatum (p < 0.0001), while no significant effect could be found in cerebellum (−4.8%, p > 0.99) indicating cerebellum as suitable reference region for mice. DVR-1 calculated using a noninvasive IDIF and an arteriovenous input function correlated significantly when considering the cerebellum as the reference region (striatum: DVR-1, r = 0.978, p < 0.0001). Additionally, strong correlations between binding potential calculated from SRTM (BPND) with DVR-1 based on IDIF (striatum: r = 0.980, p < 0.0001) and AV shunt (striatum: r = 0.987, p < 0.0001). BPND displayed higher discrimination power than VT values in determining differences between wild-types and heterozygous Q175 mice, an animal model of Huntington's disease. Furthermore, we showed high agreement between PET- and MRI-based spatial normalization approaches (striatum: r = 0.989, p < 0.0001). Finally, both spatial normalization approaches did not reveal any significant bias between test-retest scans, with a relative difference below 5%. This study indicates that noninvasive quantification of [11C]ABP688 PET imaging is reproducible and cerebellum can be used as reference region in mice.

3-Substituted 1,5-Diaryl-1 H-1,2,4-triazoles as Prospective PET Radioligands for Imaging Brain COX-1 in Monkey. Part 2: Selection and Evaluation of [11C]PS13 for Quantitative Imaging.

In our preceding paper (Part 1), we identified three 1,5-bis-diaryl-1,2,4-triazole-based compounds that merited evaluation as potential positron emission tomography (PET) radioligands for selectively imaging cyclooxygenase-1 (COX-1) in monkey and human brain, namely, 1,5-bis(4-methoxyphenyl)-3-(alkoxy)-1 H-1,2,4-triazoles bearing a 3-methoxy (PS1), a 3-(2,2,2-trifluoroethoxy) (PS13), or a 3-fluoromethoxy substituent (PS2). PS1 and PS13 were labeled from phenol precursors by O-11C-methylation with [11C]iodomethane and PS2 by O-18F-fluoroalkylation with [2H2,18F]fluorobromomethane. Here, we evaluated these PET radioligands in monkey. All three radioligands gave moderately high uptake in brain, although [2H2,18F]PS2 also showed undesirable radioactivity uptake in skull. [11C]PS13 was selected for further evaluation, mainly based on more favorable brain kinetics than [11C]PS1. Pharmacological preblock experiments showed that about 55% of the radioactivity uptake in brain was specifically bound to COX-1. An index of enzyme density, VT, was well identified from serial brain scans and from the concentrations of parent radioligand in arterial plasma. In addition, VT values were stable within 80 min, suggesting that brain uptake was not contaminated by radiometabolites. [11C]PS13 successfully images and quantifies COX-1 in monkey brain, and merits further investigation for imaging COX-1 in monkey models of neuroinflammation and in healthy human subjects.

Positron Emission Tomography Studies of the Glial Cell Marker Translocator Protein in Patients With Psychosis: A Meta-analysis Using Individual Participant Data

BackgroundAccumulating evidence suggests that the immune system may be an important target for new treatment approaches in schizophrenia. Positron emission tomography and radioligands binding to the translocator protein (TSPO), which is expressed in glial cells in the brain including immune cells, represents a potential method for patient stratification and treatment monitoring. This study examined whether patients with first-episode psychosis and schizophrenia had altered TSPO levels compared with healthy control subjects. MethodsPubMed was searched for studies comparing patients with psychosis with healthy control subjects using second-generation TSPO radioligands. The outcome measure was total distribution volume (VT), an index of TSPO levels, in frontal cortex, temporal cortex, and hippocampus. Bayes factors (BFs) were applied to examine the relative support for higher, lower, or no difference in patients’ TSPO levels compared with healthy control subjects. ResultsFive studies, with 75 participants with first-episode psychosis or schizophrenia and 77 healthy control subjects, were included. BFs showed strong support for lower VT in patients relative to no difference (all BFs > 32), or relative to higher VT (all BFs > 422), in all brain regions. From the posterior distributions, mean patient–control differences in standardized VT values were −0.48 for frontal cortex (95% credible interval [CredInt] = −0.88 to 0.09), −0.47 for temporal cortex (CredInt = −0.87 to −0.07), and −0.63 for hippocampus (CredInt = −1.00 to −0.25). ConclusionsThe lower levels of TSPO observed in patients may correspond to altered function or lower density of brain immune cells. Future studies should focus on investigating the underlying biological mechanisms and their relevance for treatment.

Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes.

Previous studies demonstrated the utility of [18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ) as a positron emission tomography (PET) radiotracer for the vesicular monoamine transporter type 2 (VMAT2) to quantify beta cell mass in healthy control (HC) and type 1 diabetes mellitus (T1DM) groups. Quantification of specific binding requires measurement of non-displaceable uptake. Our goal was to identify a reference tissue (renal cortex or spleen) to quantify pancreatic non-specific binding of [18F]FP-(+)-DTBZ with the inactive enantiomer, [18F]FP-(-)-DTBZ. This was the first human study of [18F]FP-(-)-DTBZ. Six HCs and four T1DM patients were scanned on separate days after injection of [18F]FP-(+)-DTBZ or [18F]FP-(-)-DTBZ. Distribution volumes (VT) and standardized uptake values (SUVs) were compared between groups. Three methods for calculation of non-displaceable uptake (VND) or reference SUV were applied: (1) use of [18F]FP-(+)-DTBZ reference VT as VND, assuming VND is uniform across organs; (2) use of [18F]FP-(-)-DTBZ pancreatic VT as VND, assuming that VND is uniform between enantiomers in the pancreas; and (3) use of a scaled [18F]FP-(+)-DTBZ reference VT as VND, assuming that a ratio of non-displaceable uptake between organs is uniform between enantiomers. Group differences in VT (or SUV), binding potential (BPND), or SUV ratio (SUVR) were estimated using these three methods. [18F]FP-(-)-DTBZ VT values were different among organs, and VT(+) and VT(-) were also different in the renal cortex and spleen. Method 3 with the spleen to estimate VND (or reference SUV) gave the highest non-displaceable uptake and the largest HC vs. T1DM group differences. Significant group differences were also observed in VT (or SUV) with method 1 using spleen. SUV was affected by differences in the input function between groups and between enantiomers. Non-displaceable uptake was different among organs and between enantiomers. Use of scaled spleen VT values for VND is a suitable method for quantification of VMAT2 in the pancreas.

Impact of delivered tidal volume on the occurrence of intraventricular haemorrhage in preterm infants during positive pressure ventilation in the delivery room

Background and objectivesDelivery of inadvertent high tidal volume (VT) during positive pressure ventilation (PPV) in the delivery room is common. High VT delivery during PPV has been associated with haemodynamic...

Severe Traumatic Brain Injury.

Background: Inadvertent hyperventilation is associated with poor outcomes from traumatic brain injury (TBI). Hypocapnic cerebral vasoconstriction is well described and causes an immediate and profound decrease in cerebral perfusion. The hemodynamic effects of positive-pressure ventilation (PPV) remain incompletely understood but may be equally important, particularly in the hypovolemic patient with TBI. Objective: Preliminary report on the application of a previously described mathematical model of perfusion and ventilation to prehospital data to predict intrathoracic pressure. Methods: Ventilation data from 108 TBI patients (76 ground transported, 32 helicopter transported) were used for this analysis. Ventilation rate (VR) and end-tidal carbon dioxide (PetCO2) values were used to estimate tidal volume (VT). The values for VR and estimated VT were then applied to a previously described mathematical model of perfusion and ventilation. This model allows input of various lung parameters to define a pressure–volume relationship, then derives mean intrathoracic pressure (MITP) for various VT and VR values. For this analysis, normal lung parameters were utilized. Separate analyses were performed assuming either fixed or variable PaCO2–PetCO2 differences. Ground and air medical patients were compared with regard to VR, PetCO2, estimated VT, and predicted MITP. Results: A total of 10,647 measurements were included from the 108 TBI patients, representing Received July 11, 2014 from the Department of Emergency Medicine, University of California at San Diego, La Jolla, California (DPD, SAA, GV, JVD), School of Medicine, University of California San Diego, La Jolla, California (KS), Division of Cardiology, University of California San Diego, La Jolla, California (RDH), Division of Cardiology, The Ohio State University, Columbus, Ohio (RDH), Department of Anesthesiology (AM) and Division of Pulmonary and Critical Care (RS), University of California at San Diego, La Jolla, California, and Rural/Metro Ambulance, San Diego, California, and San Diego Department of Fire–Rescue, San Diego, California (RF, CB, JVD). Accepted for publication August 4, 2014. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This paper was presented orally at the Resuscitation Science Symposium, 2011. Address correspondence to Steve A. Aguilar, MD, UC San Diego Emergency Medicine, 200 West Arbor Drive #8676, San Diego, CA 92103, USA. E-mail: SteveAguilarMD@gmail.com doi: 10.3109/10903127.2014.959228 about 13 minutes of ventilation per patient. Mean VR values were higher for ground patients versus air patients (21.6 vs. 19.7 breaths/min; p < 0.01). Estimated VT values were similar for ground and air patients (399 mL vs. 392 mL; p = NS) in the fixed model but not the variable (636 vs. 688 mL, respectively; p < 0.01). Mean PetCO2 values were lower for ground versus air patients (30.6 vs. 33.8 mmHg; p < 0.01). Predicted MITP values were higher for ground versus air patients, assuming either fixed (9.0 vs. 8.1 mmHg; p < 0.01) or variable (10.9 vs. 9.7 mmHg; p < 0.01) PaCO2–PetCO2 differences. Conclusions: Predicted MITP values increased with ventilation rates. Future studies to externally validate this model are warranted.

Mitochondrial Complex I Deficit in the Olfactory Systems of Age-related Neurodegenerative Monkey Models: A PET Study using 18F-BCPP-EF

Objective: Dysfunction of olfactory bulb area (OBA) is reported in several types of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Although pathophysiological mechanisms responsible for changes in olfactory function remain unclear, the quantitative parameters for olfactory function are expected for diagnose of neurodegenerative diseases. We developed a novel probe for positron emission tomography (PET), 18F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one (18F-BCPP-EF), for quantitative analysis of mitochondrial complex I (MC-I) activity in the living brain. In the present study, the applicability of 18F-BCPP-EF to predict age-related neurodegenerative damage in the monkey brain as an MC-I deficit in the OBA was investigated. Methods: PET measurements with 11C-PiB for amyloid--β (Aβ), 11C-DPA-713 for translocator protein (TSPO) and 18F-BCPP-EF were performed in aged monkeys. The binding specificity of 18F-BCPP-EF to MC-I in the OBA was evaluated with rotenone, a specific MC-1 inhibitor, in young animals. 11C-PiB binding to Aβ and 11C-DPA-713 binding to TSPO were calculated as standard uptake value ratios (SUVRs). The total distribution volume (VT) of 18F-BCPP-EF was calculated using a Logan graphical analysis using metabolite-corrected plasma input function, and correlations between the olfactory VT of 18F-BCPP-EF and SUVRs of 11C-PiB or 11C-DPA-713 in several brain regions were analyzed. Results: Pre-dosing of rotenone resulted in the significant reduction of VT values in all brain regions including the OBA. MC-I activity in the OBA exhibited age-related reduction, which positively correlated with MC-I activity in the olfactory-related and cortical regions. OBA MC-I and TSPO as measured using 11C-DPA-713 were inversely correlated in the olfactory-related and cortical regions, but association between OBA MC-I and Aβ deposition as measured using 11C-PiB were observed only in olfactory-related regions. Conclusion: The present study demonstrated that OBA MC-I activity could be a potential predictive parameter of neurodegenerative damages related Aβ deposition and TSPO/neuroinflammation in the living brain.

Predicting Extubation Outcome by Cough Peak Flow Measured Using a Built-in Ventilator Flow Meter.

Successful weaning from mechanical ventilation depends on the patient's ability to cough efficiently. Cough peak flow (CPF) could predict extubation success using a dedicated flow meter but required patient disconnection. We aimed to predict extubation outcome using an overall model, including cough performance assessed by a ventilator flow meter. This was a prospective observational study conducted from November 2014 to October 2015. Before and after a spontaneous breathing trial, subjects were encouraged to cough as strongly as possible before freezing the ventilator screen to assess CPF and tidal volume (VT) in the preceding inspiration. Early extubation success rate was defined as the proportion of subjects not re-intubated 48 h after extubation. Diagnostic performance of CPF and VT was assessed by using the area under the curve of the receiver operating characteristic curve. Cut-off values for CPF and VT were defined according to median values and used to describe the performance of a predictive test combining them with risk factors of early extubation failure. Among 673 subjects admitted, 92 had a cough assessment before extubation. For the 81 subjects with early extubation success, the median CPF was -67.7 L/min, and median VT was 0.646 L. For the 11 subjects with early extubation failure, the median CPF was -57.3 L/min, and median VT was 0.448 L. Area under the curve was 0.61 (95% CI 0.37-0.83) for CPF and 0.64 (95% CI 0.42-0.84) for CPF/VT combined. After dichotomization (CPF < -60 L/min or VT > 0.55 L), there was a synergistic effect to predict early extubation success (P < .001). The predictive value of success reached 94.2% for CPF/VT combined. The overall model including pH before extubation < 7.45 reached a 66.7% predictive value of failure. CPF measured using the flow meter of an ICU ventilator was able to predict extubation success and to build a composite score to predict extubation failure. The results were close to that found in previous studies that used a dedicated flow meter. This could help to identify high-risk subjects to prevent extubation failure. (ClinicalTrials.gov registration NCT02847221.).

Evaluation of Simulated Ventilation Techniques With the Upright and Conventional Self-Inflating Neonatal Resuscitators.

The study assessed the impact of simulated ventilation techniques using upright and conventional self-inflating neonatal resuscitators on delivered tidal volume (VT) and pressure. We analyzed videos of participants ventilating a manikin using an upright (upright, n = 33) and a conventional resuscitator (conventional, n = 32) under normal and low lung compliance. Mask hold, number of fingers squeezing the bag, and degree of bag squeeze were compared with VT and peak inspiratory pressure (PIP). VT and PIP values were higher when using the upright resuscitator than when using the conventional resuscitator. With low compliance, differences in VT were insignificant except with the use of the OK/C hold, (upright, 29.6 ± 4.0 mL, vs conventional, 24.8 ± 6.0 mL, P = .02). PIP was significantly higher when using the upright resuscitator with the OK hold (upright, 36.3 ± 4.4 mL, vs conventional, 30.3 ± 6.6 mL, P = .009) and when the bag was squeezed by more than half (upright, 33.8 ± 16.3 mL, vs conventional, 29.3 ± 9.5 mL, P = .046). With normal compliance, VT was high with both resuscitators, being significantly higher when using the upright resuscitator with the OK hold (upright, 64.3 ± 9.5 mL, vs conventional, 45.8 ± 9.4 mL; P < .001), and when the bag was squeezed using more than 2 fingers (upright, 58.0 ± 17.2 mL, vs conventional, 45.7 ± 12.6 mL, P = .01) and by more than half (upright, 58.7 ± 16.6 mL, vs conventional, 45.8 ± 12.2 mL, P = .004). PIP, too, was significantly higher when using the upright resuscitator with the OK hold (upright, 29.3 ± 3.5 mL, vs conventional, 21.5 ± 4.0 mL, P = <.001) and when the bag was squeezed using more than 2 fingers (upright, 27.2 ± 7.0 mL, vs conventional, 21.6 ± 5.7 mL, P = .005), and by more than half (upright, 27.6 ± 6.6 mL, vs conventional, 21.7 ± 5.4 mL, P = .001). Improved mask design, larger bag volume, and upright orientation of the upright resuscitator likely contributed to higher VT and PIP. However, high VT was observed with both resuscitators, possibly due to excessive squeezing of the bag, especially during low compliance. Thus, the design of the resuscitator and manner in which the device is utilized can both significantly influence the VT and PIP attained.

Reaction-induced grain boundary cracking and anisotropic fluid flow during prograde devolatilization reactions within subduction zones

Devolatilization reactions during prograde metamorphism are a key control on the fluid distribution within subduction zones. Garnets in Mn-rich quartz schist within the Sanbagawa metamorphic belt of Japan are characterized by skeletal structures containing abundant quartz inclusions. Each quartz inclusion was angular-shaped, and showed random crystallographic orientations, suggesting that these quartz inclusions were trapped via grain boundary cracking during garnet growth. Such skeletal garnet within the quartz schist formed related to decarbonation reactions with a positive total volume change (∆V t > 0), whereas the euhedral garnet within the pelitic schists formed as a result of dehydration reaction with negative ∆V t values. Coupled hydrological–chemical–mechanical processes during metamorphic devolatilization reactions were investigated by a distinct element method (DEM) numerical simulation on a foliated rock that contained reactive minerals and non-reactive matrix minerals. Negative ∆V t reactions cause a decrease in fluid pressure and do not produce fractures within the matrix. In contrast, a fluid pressure increase by positive ∆V t reactions results in hydrofracturing of the matrix. This fracturing preferentially occurs along grain boundaries and causes episodic fluid pulses associated with the development of the fracture network. The precipitation of garnet within grain boundary fractures could explain the formation of the skeletal garnet. Our DEM model also suggests a strong influence of reaction-induced fracturing on anisotropic fluid flow, meaning that dominant fluid flow directions could easily change in response to changes in stress configuration and the magnitude of differential stress during prograde metamorphism within a subduction zone.

Measurements of entanglement over a kilometric distance to test superluminal models of Quantum Mechanics: preliminary results.

As shown in the EPR paper (Einstein, Podolsky e Rosen, 1935), Quantum Mechanics is a non-local Theory. The Bell theorem and the successive experiments ruled out the possibility of explaining quantum correlations using only local hidden variables models. Some authors suggested that quantum correlations could be due to superluminal communications that propagate isotropically with velocity vt > c in a preferred reference frame. For finite values of vt and in some special cases, Quantum Mechanics and superluminal models lead to different predictions. So far, no deviations from the predictions of Quantum Mechanics have been detected and only lower bounds for the superluminal velocities vt have been established. Here we describe a new experiment that increases the maximum detectable superluminal velocities and we give some preliminary results.

Investigation of Regional Blood-Brain Barrier Integrity and Cerebral Efflux Transporter Function in Patients with Neuroepithelial Tumors by Means of [11C] Tariquidar Pet

At the human blood-brain barrier (BBB) high levels of efflux transporters, such as P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), are expressed, which restrict the brain distribution of many drugs. The pharmacological treatment of brain tumors is often hampered by the impermeability of the BBB to anticancer drugs. It has been shown that the BBB may become disrupted in central necrotic parts of high-grade gliomas, leading to higher drug concentrations as compared to tumor-free brain tissue. In this study [11C]tariquidar, a drug-like radiotracer, which is subject to efflux transport by ABCB1 and ABCG2 at the human BBB, is used to study regional BBB integrity and cerebral efflux transporter function in patients with neuroepithelial tumors of the central nervous system (CNS). Seven patients diagnosed with a neuroepithelial tumor and elected for neurosurgery underwent a 60-min dynamic [11C]tariquidar brain PET scan and simultaneous arterial blood sampling. Four regions of interest (tumor, tumor rim, contralateral as well as ipsilateral tumor-free brain area) were delineated on MR-co-registered PET images. Logan graphical analysis was used to estimate the total distribution volume (VT) as a parameter of [11C]tariquidar distribution from blood to different brain regions. In all patients, brain distribution of [11C]tariquidar was very low, which was consistent with ABCB1/ABCG2-mediated efflux transport at the BBB. There were no significant differences in [11C]tariquidar VT values between tumor tissue and tumor-free tissue and between the central part of the tumor and the tumor rim. In 4 patients, VT values were lower in tumor tissue as compared to contralateral tumor-free brain tissue (-89% ± 78%, range: -22% to -200%). In 3 patients, VT values were higher in tumor tissue as compared with contralateral tumor-free brain tissue (+27% ± 14%, range: +13% to +40%). We found no significant differences in distribution of [11C]tariquidar to tumor tissue and tumor-free tissue, which argues against a major BBB disruption in these patients and suggests that anticancer drugs transported by ABCB1 and ABCG2, may not reach the tumor tissue in sufficiently high and therapeutically effective concentrations.