Generative Adversarial Networks for Brain MRI Synthesis: Impact of Training Set Size on Clinical Application.

We evaluated the impact of training set size on generative adversarial networks (GANs) to synthesize brain MRI sequences. We compared three sets of GANs trained to generate pre-contrast T1 (gT1) from post-contrast T1 and FLAIR (gFLAIR) from T2. The baseline models were trained on 135 cases; for this study, we used the same model architecture but a larger cohort of 1251 cases and two stopping rules, an early checkpoint (early models) and one after 50 epochs (late models). We tested all models on an independent dataset of 485 newly diagnosed gliomas. We compared the generated MRIs with the original ones using the structural similarity index (SSI) and mean squared error (MSE). We simulated scenarios where either the original T1, FLAIR, or both were missing and used their synthesized version as inputs for a segmentation model with the original post-contrast T1 and T2. We compared the segmentations using the dice similarity coefficient (DSC) for the contrast-enhancing area, non-enhancing area, and the whole lesion. For the baseline, early, and late models on the test set, for the gT1, median SSI was .957, .918, and .947; median MSE was .006, .014, and .008. For the gFLAIR, median SSI was .924, .908, and .915; median MSE was .016, .016, and .019. The range DSC was .625-.955, .420-.952, and .610-.954. Overall, GANs trained on a relatively small cohort performed similarly to those trained on a cohort ten times larger, making them a viable option for rare diseases or institutions with limited resources.

Exploring the relationship between bacterial genera and lipid metabolism in bovine rumen.

The rumen is characterised by a complex microbial ecosystem, which is particularly active in lipid metabolism. Several studies demonstrated a role of diet and breed on bacterial community profile, with the effect on metabolic pathways. Despite the knowledge achieved on metabolism and the bacterial profile, little is known about the relationship between individual bacteria and metabolic pathways. Therefore, a multivariate approach was used to search for possible relationships between bacteria and products of several pathways. The correlation between rumen bacterial community composition and rumen lipid metabolism was assessed in 40 beef steers (20 Maremmana and 20 Aubrac) reared with the same system and fed the same diet. A canonical discriminant analysis combined with a canonical correlation analysis (CCA) was performed to explore this correlation. The variables showing a Pearson correlation higher than 0.6 as absolute value and significant were retained for CCA considering the relationship of bacterial composition with several metabolic pathways. The results indicated that some bacterial genera could have significant impacts on the presence of several fatty acids. However, the relationship between genera and fatty acid changes according to the breed, demonstrating that the metabolic pathways change according to the host genetic background, related to breed evolution, although there is also an intra-breed genetic background which should not be ignored. In Maremmana, Succiniclasticum and Rikenellaceae_RC9_gut_group showed a high positive correlation with dimethylacetals (DMAs) DMAC13:0, DMAC14:0, DMAC14:0iso, DMAC15:0, DMAC15:0iso, and DMAC18:0. Prevotellaceae_UCG-003 correlates with C18:3c9c12c15 and C18:1t11, while Fibrobacter and Succiniclasticum correlate with C18:2c9t11 and Lachnospiraceae_NK3A20_group correlates with C18:1c12. Prevotellaceae_UCG-003, Ruminococcaceae_UCG-010, and Oribacterium showed a positive correlation with C13:0iso, and C17:0. Conversely, in Aubrac, Treponema_2 and Rikenellaceae_RC9_gut_group correlated with DMAC14:0iso, DMAC16:0iso, DMAC17:0iso, while Ruminococcaceae_UCG-010, Christensenellaceae_R-7_group and Ruminococcaceae_NK4A214_group correlated with DMAC18:1t11, DMAC14:0, DMAC18:1c12. Acetitomaculum correlated with C18:2c9c12, C18:1c12, C18:1c13, C18:1t12 and Lachnospiraceae_NK3A20_group with C18:1t6-8 and C18:1t9. Saccharofermentas, Ruminococcaceae_UCG-010 and Rikenellaceae_RC9_gut_group correlated with C18:2c9t11 while, Prevotellaceae_UCG-001 and Ruminococcus_1 correlated with C14:0iso, C15:0, C15:0iso, C17:0. Saccharofermentans, Rikenellaceae_RC9_gut_group, Ruminococcaceae_NK4A214_group, and Ruminococcaceae_UCG-010 correlated with C13:1c12 and C16:0iso. These results lead to hypothesise a possible association between several metabolic pathways and one or a few bacterial genera. If these associations are confirmed by further investigations that verify the causality of a bacterial genus with a particular metabolic process, it will be possible to deepen the knowledge on the activity of the rumen population in lipid metabolism. This approach appears to be a promising tool for uncovering the correlation between bacterial genera and products of rumen lipid metabolism.

Safety and preliminary activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody gatipotuzumab with the anti-EGFR tomuzotuximab in patients with refractory solid tumors.

BACKGROUND: The phase I GATTO study (NCT03360734) explored the feasibility, tolerability and preliminary activity of combining gatipotuzumab, a novel humanized monoclonal antibody binding to the tumor-associated epitope of mucin 1 (TA-MUC1) and an anti-epidermal growth factor receptor (anti-EGFR) antibody in refractory solid tumors. PATIENTS AND METHODS: Initially the study enrolled primary phase (PP) patients with EGFR-positive metastatic solid tumors, for whom no standard treatment was available. Patients received gatipotuzumab administered at 1400 mg every 2 weeks, 6 weeks after the start of the glyco-optimized anti-EGFR antibody tomuzotuximab at 1200 mg every 2 weeks. As this regimen was proven safe, enrollment continued in an expansion phase (EP) of patients with refractory metastatic colorectal cancer, non-small-cell lung cancer, head and neck cancer and breast cancer. Tomuzotuximab and gatipotuzumab were given at the same doses and gatipotuzumab treatment started 1 week after the first dose of the anti-EGFR antibody. Additionally, investigators could use a commercial anti-EGFR antibody in place of tomuzotuximab. RESULTS: A total of 52 patients were enrolled, 20 in the PP and 32 in the EP. The combined treatment was well tolerated and no dose-limiting toxicity was observed in the whole study, nor related serious adverse event or death. Preliminary activity of the combination was observed, with one and four RECIST partial responses in the PP and EP, all in colorectal cancer patients. The trial was accompanied by a comprehensive translational research program for identification of biomarkers, including soluble TA-MUC1 (sTA-MUC1) in serum. In the EP, patients with baseline sTA-MUC1 levels above the median appeared to have improved progression-free survival and overall survival. CONCLUSIONS: Combination of a TA-MUC1-targeting antibody and an EGFR-targeting antibody is safe and feasible. Interesting antitumor activity was observed in heavily pretreated patients. Future studies should test this combination together with chemotherapy and explore the potential of sTA-MUC1 as a companion biomarker for further development of the combination.

Quantitative muscle mass biomarkers are independent prognosis factors in primary central nervous system lymphoma: The role of L3-skeletal muscle index and temporal muscle thickness.

OBJECTIVE: To investigate the role of quantitative muscle biomarkers assessed with skeletal muscle index at the third lumbar vertebra (L3-SMI) and temporal muscle thickness (TMT) in predicting progression-free and overall survival in patients with primary central nervous system lymphoma (PCNSL) undergoing first-line high-dose methotrexate-based chemotherapy. METHODS: L3-SMI and TMT were calculated on abdominal CT and brain high-resolution 3D-T1-weighted MR images, respectively, using predefined validated methods. Standardized sex-specific cut-off values were used to divide patients in different risk categories. Kaplan-Meier plots were calculated, and survival analysis was performed using log-rank tests, univariate, and multivariable Cox-regression models, calculating hazard ratios (HR) and 95% confidence intervals (CI), also adjusting for potential confounders (age, sex, and performance status). RESULTS: Forty-three patients were included in this study. Median follow-up was 23 months (interquartile range 12-40); at median follow-up, rates of progression-free and overall survival for the cohort were 46% and 57%, respectively. Thirteen (30%) and 11 (26%) patients showed L3-SMI or TMT values below the predefined cut-offs. In Cox-regression multivariable analysis patients with low L3-SMI or TMT showed significantly worse progression-free (HR 4.40, 95% CI 1.66-11.61, p = 0.003; HR 4.40, 95% CI 1.68-11.49, p = 0.003, respectively) and overall survival (HR 3.16, 95% CI 1.09-9.11, p = 0.034; HR 4.93, 95% CI 1.78-13.65, p = 0.002, respectively) compared to patients with high L3-SMI or TMT. CONCLUSIONS: Quantitative muscle mass evaluation assessed by both L3-SMI and TMT is a promising tool to identify PCNSL patients at high risk of negative outcome. Confirmatory studies on larger independent series are warranted.

Impact of exclusive e-cigarettes and heated tobacco products use on muco-ciliary clearance.

BACKGROUND: Tobacco smoking impairs mucociliary clearance (MCC) efficiency as shown by prolonged saccharin test transit time (STTT). Avoiding exposure to tobacco smoke from combustible cigarettes may restore MCC function and former smokers have been shown to exhibit similar STTT as never smokers. The impact on STTT of switching from smoking to combustion-free tobacco products such as e-cigarettes (ECs) and heated tobacco products (HTPs) is not known. METHODS: We report STTT of exclusive EC and HTP users. Test results were compared with those obtained in current, former, and never smokers. RESULTS: STTT were obtained from 39 current, 40 former, 40 never smokers, and from 20 EC and 20 HTP users. Comparison of STTT values showed significant difference among the five study groups (p < 0.00001) with current smokers having a median [interquartile range (IQR)] STTT of 13.15 min, which was significantly longer compared with that of all other study groups. In particular, compared with former (7.26 min) and never smokers (7.24 min), exclusive EC users and exclusive HTP users had similar STTT at 7.00 and 8.00 min, respectively. CONCLUSION: Former smokers who have switched to exclusive regular use of combustion-free nicotine delivery systems (i.e., ECs and HTPs) exhibit similar saccharin transit time as never and former smokers. This suggests that combustion-free nicotine delivery technologies are unlikely to have detrimental effects on MCC function.

Assessment of the Membranous Labyrinth in Infants Using a Heavily T2-weighted 3D FLAIR Sequence without Contrast Agent Administration.

BACKGROUND AND PURPOSE: Imaging is fundamental to assessing the acoustic pathway in infants with congenital deafness. We describe our depiction of the membranous labyrinth in infants using the heavily T2-weighted 3D FLAIR sequence without a contrast agent. MATERIALS AND METHODS: We retrospectively reviewed 10 infants (20 ears) (median term equivalent age: 2 weeks; IQR: 1-5 weeks) who had undergone brain MR imaging including a noncontrast heavily T2-weighted 3D FLAIR scan of the temporal bone. For each ear, 3 observers analyzed, in consensus, the saccule, the utricle, and the 3 ampullae, assessing the visibility (score 0, not appreciable; score 1, visible without well-defined boundaries; score 2, visible with well-defined boundaries) and morphology ("expected" or "unexpected" compared with adults). The heavily T2-weighted 3D FLAIR sequence was scored for overall quality (score 0, inadequate; score 1, adequate but with the presence of image degradation; score 2, adequate). RESULTS: Six (60%) MR examinations were considered adequate (score 1 or 2). The saccule was visible in 10 ears (83.3%) with an expected morphology in 9 ears (90%). In 1 ear of an infant with congenital deafness, the saccule showed an unexpected morphology. The utricle was visible as expected in 12 ears (100%). The lateral ampulla was visible in 5 ears (41.6%), the superior ampulla was visible in 6 ears (50.0%), and the posterior ampulla was visible in 6 ears (50.0%), always with expected morphology (100%). CONCLUSIONS: MR imaging can depict the membranous labyrinth in infants using heavily T2-weighted 3D FLAIR without an injected contrast agent, but the sequence acquisition time reduces its feasibility in infants undergoing MR studies during natural sleep.

COVID-19-Associated PRES-like Encephalopathy with Perivascular Gadolinium Enhancement.

We describe the case of a 63-year-old woman who developed a coronavirus disease 2019-associated acute encephalopathy with perivascular gadolinium enhancement.

Structural brain anomalies in Cri-du-Chat syndrome: MRI findings in 14 patients and possible genotype-phenotype correlations.

INTRODUCTION: Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978. The classic phenotype includes a characteristic cry, peculiar facies, microcephaly, growth retardation, hypotonia, speech and psychomotor delay and intellectual disability. A wide spectrum of clinical manifestations can be attributed to differences in size and localization of the 5p deletion. Several critical regions related to some of the main features (such as cry, peculiar facies, developmental delay) have been identified. The aim of this study is to further define the genotype-phenotype correlations in CdCS with particular regards to the specific neuroradiological findings. PATIENTS AND METHODS: Fourteen patients with 5p deletions have been included in the present study. Neuroimaging studies were conducted using brain Magnetic Resonance Imaging (MRI). Genetic testing was performed by means of comparative genomic hybridization (CGH) array at 130 kb resolution. RESULTS: MRI analyses showed that isolated pontine hypoplasia is the most common finding, followed by vermian hypoplasia, ventricular anomalies, abnormal basal angle, widening of cavum sellae, increased signal of white matter, corpus callosum anomalies, and anomalies of cortical development. Chromosomal microarray analysis identified deletions ranging in size from 11,6 to 33,8 Mb on the short arm of chromosome 5. Then, we took into consideration the overlapping and non-overlapping deleted regions. The goal was to establish a correlation between the deleted segments and the neuroradiological features of our patients. CONCLUSIONS: Performing MRI on all the patients in our cohort, allowed us to expand the neuroradiological phenotype in CdCS. Moreover, possible critical regions associated to characteristic MRI findings have been identified.

Multivariate factor analysis of milk fatty acid composition in relation to the somatic cell count of single udder quarters.

The present study investigated whether the fatty acid composition of milk changes in relation to an increase in the milk somatic cell count (SCC) of separate udder quarters. We investigated the potential of multivariate factor analysis to extract metabolic evidence from data on the quantity and quality of milk of quarters characterized by different SCC levels. We collected data from individual milk samples taken from single quarters of 49 Italian Holstein cows from the same dairy farm. Factor analysis was carried out on 64 individual fatty acids. In line with a previous study on multivariate factor analysis, a variable was considered to be associated with a specific factor if the absolute value of its correlation with the factor was ≥0.60. Seven factors were extracted that explained the following groups of fatty acids or functions: de novo synthesis, energy balance, uptake of dietary fatty acids, biohydrogenation, short-chain fatty acids, very long chain fatty acids, and odd- and branched-chain fatty acids. An ANOVA of factor scores highlighted the significant effects of the SCC level on de novo fatty acids and biohydrogenation. The de novo fatty acid factor decreased significantly with a high level of SCC, from just 10,000 cells/mL, whereas the biohydrogenation factor showed a significantly higher level in quarters with SCC levels greater than 400,000 cells/mL. This statistical approach enabled us to reduce the number of variables to a few latent factors with biological significance and to represent groups of fatty acids with a common origin and function. Multivariate factor analysis could therefore be key to studying the influence of SCC on the lipid metabolism of single quarters. This approach also demonstrated the metabolic differences between quarters of the same animal showing a different level of SCC.

Infrarenal versus supraceliac aorto-hepatic arterial revascularisation in adult liver transplantation: multicentre retrospective study.

When the standard arterial reconstruction is not feasible during liver transplantation (LT), aorto-hepatic arterial reconstruction (AHAR) can be the only solution to save the graft. AHAR can be performed on the infrarenal (IR) or supraceliac (SC) tract of the aorta, but the possible effect on outcome of selecting SC versus IR reconstruction is still unclear. One hundred and twenty consecutive patients who underwent liver transplantation with AHAR in six European centres between January 2003 and December 2018 were retrospectively analysed to ascertain whether the incidence of hepatic artery thrombosis (HAT) was influenced by the type of AHAR (IR-AHAR vs. SC-AHAR). In 56/120 (46.6%) cases, an IR anastomosis was performed, always using an interposition arterial conduit. In the other 64/120 (53.4%) cases, an SC anastomosis was performed; an arterial conduit was used in 45/64 (70.3%) cases. Incidence of early (≤ 30 days) HAT was in 6.2% (4/64) in the SC-AHAR and 10.7% (6/56) IR-AHAR group (p = 0.512) whilst incidence of late HAT was significantly lower in the SC-AHAR group (4.7% (3/64) vs 19.6% (11/56) - p = 0.024). IR-AHAR was the only independent risk factor for HAT (exp[B] = 3.915; 95% CI 1.400-10.951; p = 0.009). When AHAR is necessary at liver transplantation, the use of the supraceliac aorta significantly reduces the incidence of hepatic artery thrombosis and should therefore be recommended whenever possible.

Prescribing Patterns of Psychotropic Drugs and Risk of Violent Behavior: A Prospective, Multicenter Study in Italy.

BACKGROUND: This prospective cohort study aimed at evaluating patterns of polypharmacy and aggressive and violent behavior during a 1-year follow-up in patients with severe mental disorders. METHODS: A total of 340 patients (125 inpatients from residential facilities and 215 outpatients) were evaluated at baseline with the Structured Clinical Interview for DSM-IV Axis I and II, Brief Psychiatric Rating Scale, Specific Levels of Functioning scale, Brown-Goodwin Lifetime History of Aggression, Buss-Durkee Hostility Inventory, Barratt Impulsiveness Scale, and State-Trait Anger Expression Inventory-2. Aggressive behavior was rated every 15 days with the Modified Overt Aggression Scale and treatment compliance with the Medication Adherence Rating Scale. RESULTS: The whole sample was prescribed mainly antipsychotics with high levels of polypharmacy. Clozapine prescription and higher compliance were associated with lower levels of aggressive and violent behavior. Patients with a history of violence who took clozapine were prescribed the highest number of drugs. The patterns of cumulative Modified Overt Aggression Scale mean scores of patients taking clozapine (n = 46), other antipsychotics (n = 257), and no antipsychotics (n = 37) were significantly different (P = .001). Patients taking clozapine showed a time trend at 1-year follow-up (24 evaluations) indicating a significantly lower level of aggressive behavior. Patient higher compliance was also associated with lower Modified Overt Aggression Scale ratings during the 1-year follow-up. CONCLUSION: Both inpatients and outpatients showed high levels of polypharmacy. Clozapine prescription was associated with lower Modified Overt Aggression Scale ratings compared with any other antipsychotics or other psychotropic drugs. Higher compliance was associated with lower levels of aggressive and violent behavior.

Retreatability of two hydraulic calcium silicate-based root canal sealers using rotary instrumentation with supplementary irrigant agitation protocols: a laboratory-based micro-computed tomographic analysis.

AIM: To investigate the retreatability of two calcium silicate-based materials (BioRoot RCS, Septodont, Saint-Maur-des-Fossés, France and GuttaFlow Bioseal, Colténe/Whaledent AG, Langenau, Germany) using rotary instrumentation combined with supplementary irrigant agitation techniques using extracted teeth in a laboratory setting. METHODOLOGY: The root canals of extracted single-rooted mandibular premolars were prepared to size 40, .04 taper and randomly divided into two experimental groups (n = 36) depending on the root filling material. Root canals were filled with gutta-percha and GuttaFlow Bioseal (GB, group 1) or BioRoot RCS (BR, group 2), scanned using a micro-CT scanner and stored in phosphate-buffered saline for 4 months. Removal of root filling was performed with rotary instruments, and specimens were randomly allocated to one of the subgroups for supplementary irrigant agitation (n = 12): subgroup A, syringe irrigation (control); subgroup B, Tornado Brush (M.I.B, Suresnes, France) and subgroup C, ultrasonically activated irrigation. Specimens were re-scanned with micro-CT to calculate the volume of remnant root filling material. Data were analysed statistically by two-way ANOVA and post hoc Tukey's tests (P = 0.05). RESULTS: Specimens filled with GuttaFlow Bioseal were associated with a significantly smaller volume of root filling remnants compared with BioRoot RCS (P < 0.05). There was no significant difference between the supplementary irrigant agitation subgroups in the removal of GB (P > 0.05). In group 2 (BioRoot RCS), subgroups B (Tornado Brush) and C (ultrasonically activated irrigation) were associated with a significantly smaller volume of root filling remnants compared with subgroup A (syringe irrigation) (P < 0.05). There was no significant difference between subgroups B and C (P > 0.05). CONCLUSIONS: Significantly smaller volumes of root filling remnants of GuttaFlow Bioseal, than BioRoot RCS, were present after their removal with rotary instruments and irrigation. Supplementary irrigant agitation techniques were associated with smaller volumes of remnants during the removal of BioRoot RCS but not that of GuttaFlow Bioseal.

Correction to: Inert gas narcosis in scuba diving, different gases different reactions.

The original version of this article unfortunately contained a mistake.

Comparison of T1 mapping and fixed T1 method for dynamic contrast-enhanced MRI perfusion in brain gliomas.

OBJECTIVES: To compare dynamic contrast-enhanced MRI (DCE-MRI) data obtained using different prebolus T1 values in glioma grading and molecular profiling. METHODS: We retrospectively reviewed 83 cases of gliomas: 46 lower-grade gliomas (LGG; grades II and III) and 37 high-grade gliomas (HGG; grade IV). DCE-MRI maps of plasma volume fraction (Vp), extravascular-extracellular volume fraction (Ve), and tracer transfer constant from plasma to tissue (Ktrans) were obtained using a fixed T1 value of 1400 ms and a measured T1 obtained with variable flip angle (VFA). Tumour segmentations were performed and first-order histogram parameters were extracted from volumes of interest (VOIs) after co-registration with the perfusion maps. The two methods were compared using Wilcoxon matched-pairs signed-rank test and Bland-Altman analysis. Diagnostic accuracy was obtained and compared using ROC curve analysis and DeLong's test. RESULTS: Perfusion parameters obtained with the fixed T1 value were significantly higher than those obtained with the VFA. As regards diagnostic accuracy, there were no significant differences between the two methods both for glioma grading and molecular classification, except for few parameters of both methods. CONCLUSIONS: DCE-MRI data obtained with different prebolus T1 are not comparable and the definition of a prebolus T1 by T1 mapping is not mandatory since it does not improve the diagnostic accuracy of DCE-MRI. KEY POINTS: • DCE-MRI data obtained with different prebolus T1 are significantly different, thus not comparable. • The definition of a prebolus T1 by T1 mapping is not mandatory since it does not improve the diagnostic accuracy of DCE-MRI for glioma grading. • The use of a fixed T1 value represents a valid alternative to T1 mapping for DCE-MRI analysis.

CO2 Adsorption Investigation on an Innovative Nanocomposite Material with Hierarchical Porosity.

A NaX nanozeolite-geopolymer monolith, with hierarchical porosity, has been produced by a one-pot hydrothermal synthesis using metakaolin as alluminosilicate source and a sodium silicate solution as activator. Its final composition, reported in terms of oxides, is 1.3-Na2O-3.0SiO2-1Al2O3-12H2O. Its microstructural and chemical features and CO2 adsorption performance have been investigated. The microstructure of the composite is characterized by NaX zeolite nanocrystals glued by the geopolymeric binder to form a complex three-dimensional network of pores. Overall porosity resulted ~23.5%, whereas compressive strength is 16±0.7 MPa. Monolith showed BET surface area of 350 m²/g, a micropore surface area of 280 m²/g and a mesopore volume, due to the geopolymeric binder, of 0.09 cm³/g. Its CO2 adsorption capacity has been measured at the temperatures of 7, 25 and 42 °C up to 15 bar using an optimized Sievert-type (volumetric) apparatus. All the adsorption data were evaluated by Toth/Langmuir isotherm model and commercial pure NaX zeolite was used as reference. CO2 adsorption isotherms show a maximum uptake value around 21 wt% at (~7 °C) that decrease to 18 wt% at high temperature (~42 °C) passing through 19 wt% at room temperature (~25 °C). The homogeneity grade of the surface, as obtained using Toth analysis performed on the adsorption isotherm, is close to t ≅ 0.40, lower than the 0.61 obtained for pure commercial NaX zeolite, as a consequence of the binder formation. Monolith exhibits a notably higher K values and quicker saturation with respect to reference that can be ascribed to the presence of mesoporosity that provides an easier and faster transport of CO2 in the NaX nanozeolite framework. The produced composite is a potential solid adsorbent candidate in industrial process.

Inert gas narcosis in scuba diving, different gases different reactions.

PURPOSE: Underwater divers face several potential neurological hazards when breathing compressed gas mixtures including nitrogen narcosis which can impact diver's safety. Various human studies have clearly demonstrated brain impairment due to nitrogen narcosis in divers at 4 ATA using critical flicker fusion frequency (CFFF) as a cortical performance indicator. However, recently some authors have proposed a probable adaptive phenomenon during repetitive exposure to high nitrogen pressure in rats, where they found a reversal effect on dopamine release. METHODS: Sixty experienced divers breathing Air, Trimix or Heliox, were studied during an open water dive to a depth of 6 ATA with a square profile testing CFFF measurement before (T0), during the dive upon arriving at the bottom (6 ATA) (T1), 20 min of bottom time (T2), and at 5 m (1.5 ATA) (T3). RESULTS: CFFF results showed a slight increase in alertness and arousal during the deep dive regardless of the gas mixture breathed. The percent change in CFFF values at T1 and T2 differed among the three groups being lower in the air group than in the other groups. All CFFF values returned to basal values 5 min before the final ascent at 5 m (T3), but the Trimix measurements were still slightly better than those at T0. CONCLUSIONS: Our results highlight that nitrogen and oxygen alone and in combination can produce neuronal excitability or depression in a dose-related response.