High altitudes and partial pressure of arterial oxygen in patients with chronic obstructive pulmonary disease - A systematic review and meta-analysis.

IMPORTANCE: Prior study in healthy subjects has shown a reduction of partial pressure of arterial oxygen (PaO2) by -1.60 kPa/kilometre of altitude gain. However, the association of altitude-related change in PaO2 and altitude-related adverse health effects (ARAHE) in patients with chronic obstructive pulmonary disease (COPD) remain unknown. OBJECTIVE: To provide an effect size estimate for the decline in PaO2 with each kilometre of altitude gain and to identify ARAHE in relation to altitude in patients with COPD. www.crd.york.ac.uk/prospero: CRD42020217938. DATA SOURCES: A systematic search of PubMed and Embase was performed from inception to May 30, 2023. STUDY SELECTION: Peer-reviewed and prospective studies in patients with COPD staying at altitudes >1500 m providing arterial blood gases within the first 3 days at the target altitude. DATA EXTRACTION AND SYNTHESIS: Aggregate data (AD) on study characteristics were extracted, and individual patient data (IPD) were requested. Estimates were pooled using random-effects meta-analysis. MAIN OUTCOME AND MEASURES: Relative risk estimates and 95 % confidence intervals for the association between PaO2 and altitude in patients with COPD. RESULTS: Thirteen studies were included in the AD analysis, of which 6 studies (222 patients, 45.2 % female) provided IPD, thus were included in the quantitative analysis. The estimated effect size of PaO2 was -0.84 kPa [95 %CI, -0.92 to -0.76] per 1000 m of altitude gain (I2=65.0 %, P < 0.001). In multivariable regression analysis, COPD severity, baseline PaO2, age and time spent at altitude were predictors for PaO2 at altitude. Overall, 37.8 % of COPD patients experienced an ARAHE, whereas older age, female sex, COPD severity, baseline PaO2, and target altitude were predictors for the occurrence of ARAHE (area under ROC curve: 0.9275, P < 0.001). CONCLUSIONS AND RELEVANCE: This meta-analysis, providing altitude-related decrease in PaO2 and risk of ARAHE in patients with COPD ascending to altitudes >1500 m, revealed a lower altitude-related decrease in PaO2 in COPD patients compared with healthy. However, these findings might improve patient care and facilitate decisions about initiating preventive measures against hypoxaemia and ARAHE in patients with COPD planning an altitude sojourn or intercontinental flight, i.e. supplemental oxygen or acetazolamide.

Effects of ultra-high field MRI environment on cognitive performance in healthy participants.

INTRODUCTION: Ultra-high field MRI (UHF MRI) is rapidly becoming an essential part of our toolbox within health care and research studies; therefore, we need to get a deeper understanding of the physiological effects of ultra-high field. This study aims to investigate the cognitive performance of healthy participants in a 7 T (T) MRI environment in connection with subjectively experienced effects. METHODS: We measured cognitive performance before and after a 1-h 7T MRI scanning session using a Digit Symbol Substitution Test (DSST) in 42 subjects. Furthermore, a computer-based survey regarding the subjectively experienced effects in connection with the MRI examination was distributed. Similarly, two DSSTs were also performed by a control group of 40 participants. RESULTS: Even though dizziness was the strongest sensory perception in connection to the MRI scanning, we did not find any correlation between dizziness and cognitive performance. Whilst the control group improved (p=<0.001) on their second DSST the MRI group showed no significant difference (p=0.741) in the DSST before and after MRI scanning. CONCLUSION: Transient effect on cognition after undergoing MRI scanning can't be ruled out as the expected learning effect on the DSST was not observed. IMPLICATIONS FOR PRACTICE: Increasing understanding of the possible adverse effects may guide operators in performing UHF MRI in a safe way and with person-centered care. Furthermore, it can guide researchers in setting up research protocols to minimize confounding factors in their fMRI studies due to the transient adverse effects of the UHF environment.

Corrigendum: Echocardiography and extravascular lung water during 3 weeks of exposure to high altitude in otherwise healthy asthmatics.

[This corrects the article DOI: 10.3389/fphys.2023.1214887.].

Echocardiography and extravascular lung water during 3 weeks of exposure to high altitude in otherwise healthy asthmatics.

Background: Asthma rehabilitation at high altitude is common. Little is known about the acute and subacute cardiopulmonary acclimatization to high altitude in middle-aged asthmatics without other comorbidities. Methods: In this prospective study in lowlander subjects with mostly mild asthma who revealed an asthma control questionnaire score >0.75 and participated in a three-week rehabilitation program, we assessed systolic pulmonary artery pressure (sPAP), cardiac function, and extravascular lung water (EVLW) at 760 m (baseline) by Doppler-echocardiography and on the second (acute) and last day (subacute) at a high altitude clinic in Kyrgyzstan (3100 m). Results: The study included 22 patients (eight male) with a mean age of 44.3 ± 12.4 years, body mass index of 25.8 ± 4.7 kg/m2, a forced expiratory volume in 1 s of 92% ± 19% predicted (post-bronchodilator), and partially uncontrolled asthma. sPAP increased from 21.8 mmHg by mean difference by 7.5 [95% confidence interval 3.9 to 10.5] mmHg (p < 0.001) during acute exposure and by 4.8 [1.0 to 8.6] mmHg (p = 0.014) during subacute exposure. The right-ventricular-to-pulmonary-artery coupling expressed by TAPSE/sPAP decreased from 1.1 by -0.2 [-0.3 to -0.1] mm/mmHg (p < 0.001) during acute exposure and by -0.2 [-0.3 to -0.1] mm/mmHg (p = 0.002) during subacute exposure, accordingly. EVLW significantly increased from baseline (1.3 ± 1.8) to acute hypoxia (5.5 ± 3.5, p < 0.001) but showed no difference after 3 weeks (2.0 ± 1.8). Conclusion: In otherwise healthy asthmatics, acute exposure to hypoxia at high altitude increases pulmonary artery pressure (PAP) and EVLW. During subacute exposure, PAP remains increased, but EVLW returns to baseline values, suggesting compensatory mechanisms that contribute to EVLW homeostasis during acclimatization.

Sleep apnea in school-age children living at high altitude.

INTRODUCTION: Among adults, sleep apnea is more common in highlanders than in lowlanders. We evaluated the sleep apnea prevalence in children living at high altitude compared to age-matched low-altitude controls. METHODS: Healthy children, 7-14 y of age, living at 2500-3800m in the Tien Shan mountains, Kyrgyzstan, were prospectively studied in a health post at 3250m. Healthy controls of similar age living at 700-800m were studied in a University Hospital at 760m in Bishkek. Assessments included respiratory sleep studies scored according to pediatric standards, clinical examination, medical history, and the pediatric sleep questionnaire (PSQ, range 0 to 1 with increasing symptoms). RESULTS: In children living at high altitude (n = 37, 17 girls, median [quartiles] age 10.8y [9.6;13.0]), sleep studies revealed: mean nocturnal pulse oximetry 90% (89;91), oxygen desaturation index (ODI, >3% dips in pulse oximetry) 4.3/h (2.5;6.7), apnea/hypopnea index (AHI) total 1.7/h (1.0;3.6), central 1.6/h (1.0;3.3), PSQ 0.27 (0.18;0.45). In low-altitude controls (n=41, 17 girls, age 11.6y [9.5;13.0], between-groups comparison of age P=0.69) sleep studies revealed: pulse oximetry 97% (96;97), ODI 0.7/h (0.2;1.2), AHI total 0.4/h (0.1;1.0), central 0.3/h (0.1;0.7), PSQ 0.18 (0.14;0.31); P<0.05, all corresponding between-group comparisons. CONCLUSIONS: In school-age children living at high altitude, nocturnal oxygen saturation was lower, and the total and central AHI were higher compared to children living at low altitude. The greater score of sleep symptoms in children residing at high altitude suggests a potential clinical relevance of the nocturnal hypoxemia and subtle sleep-related breathing disturbances.

Effect of 5 weeks of oral acetazolamide on patients with pulmonary vascular disease: A randomized, double-blind, cross-over trial.

BACKGROUND: The carbonic anhydrase inhibitor acetazolamide stimulates ventilation through metabolic acidosis mediated by renal bicarbonate excretion. In animal models, acetazolamide attenuates acute hypoxia-induced pulmonary hypertension (PH), but its efficacy in treating patients with PH due to pulmonary vascular disease (PVD) is unknown. METHODS: 28 PVD patients (15 pulmonary arterial hypertension, 13 distal chronic thromboembolic PH), 13 women, mean±SD age 61.6±15.0 years stable on PVD medications, were randomised in a double-blind crossover protocol to 5 weeks acetazolamide (250mg b.i.d) or placebo separated by a ≥2 week washout period. Primary endpoint was the change in 6-minute walk distance (6MWD) at 5 weeks. Additional endpoints included safety, tolerability, WHO functional class, quality of life, arterial blood gases, and hemodynamics (by echocardiography). RESULTS: Acetazolamide had no effect on 6MWD compared to placebo (treatment effect: mean change [95%CI] -18 [-40 to 4]m, p=0.102) but increased arterial blood oxygenation through hyperventilation induced by metabolic acidosis. Other measures including pulmonary hemodynamics were unchanged. No severe adverse effects occurred, side effects that occurred significantly more frequently with acetazolamide vs. placebo were change in taste (22/0%), paraesthesia (37/4%) and mild dyspnea (26/4%). CONCLUSIONS: In patients with PVD, acetazolamide did not change 6MWD compared to placebo despite improved blood oxygenation. Some patients reported a tolerable increase in dyspnoea during acetazolamide treatment, related to hyperventilation, induced by the mild drug-induced metabolic acidosis. Our findings do not support the use of acetazolamide to improve exercise in patients with PVD at this dosing. GOV IDENTIFIER: NCT02755298.

Visuomotor performance at high altitude in COPD patients. Randomized placebo-controlled trial of acetazolamide.

Introduction: We evaluated whether exposure to high altitude impairs visuomotor learning in lowlanders with chronic obstructive pulmonary disease (COPD) and whether this can be prevented by acetazolamide treatment. Methods: 45 patients with COPD, living <800 m, FEV1 ≥40 to <80%predicted, were randomized to acetazolamide (375 mg/d) or placebo, administered 24h before and during a 2-day stay in a clinic at 3100 m. Visuomotor performance was evaluated with a validated, computer-assisted test (Motor-Task-Manager) at 760 m above sea level (baseline, before starting the study drug), within 4h after arrival at 3100 m and in the morning after one night at 3100 m. Main outcome was the directional error (DE) of cursor movements controlled by the participant via mouse on a computer screen during a target tracking task. Effects of high altitude and acetazolamide on DE during an adaptation phase, immediate recall and post-sleep recall were evaluated by regression analyses. www.ClinicalTrials.gov NCT03165890. Results: In 22 patients receiving placebo, DE at 3100 m increased during adaptation by mean 2.5°, 95%CI 2.2° to 2.7° (p < 0.001), during immediate recall by 5.3°, 4.6° to 6.1° (p < 0.001), and post-sleep recall by 5.8°, 5.0 to 6.7° (p < 0.001), vs. corresponding values at 760 m. In 23 participants receiving acetazolamide, corresponding DE were reduced by -0.3° (-0.6° to 0.1°, p = 0.120), -2.7° (-3.7° to -1.6°, p < 0.001) and -3.1° (-4.3° to -2.0°, p < 0.001), compared to placebo at 3100 m. Conclusion: Lowlanders with COPD travelling to 3100 m experienced altitude-induced impairments in immediate and post-sleep recall of a visuomotor task. Preventive acetazolamide treatment mitigated these undesirable effects.

MR-safety in clinical practice at 7T: Evaluation of a multistep screening process in 1819 subjects.

INTRODUCTION: MR facilities must implement and maintain adequate screening and safety procedures to ensure safety during MR examinations. The aim of this study was to evaluate a multi-step MR safety screening process used at a 7T facility regarding incidence of different types of safety risks detected during the safety procedure. METHODS: Subjects scheduled for an MR examination and having entered the 7T facility during 2016-2019 underwent a pre-defined multi-step MR safety screening process. Screening documentation of 1819 included subjects was reviewed, and risks identified during the different screening steps were compiled. These data were also related to documented decisions made by a 7T MR safety committee and reported MR safety incidents. RESULTS: Passive or active implants (n = 315) were identified in a screening form and/or an additional documented interview in 305 subjects. Additional information not previously self-reported by the subject, regarding implants necessitating safety decisions performed by the staff was revealed in the documented interview in 102 subjects (106 items). In total, the 7T MR safety committee documented a decision in 36 (2%) of the included subjects. All of these subjects were finally cleared for scanning. CONCLUSION: A multi-step screening process allows a thorough MR screening of subjects, avoiding safety incidents. Different steps in the process allow awareness to rise and items to be detected that were missed in earlier steps. IMPLICATIONS FOR PRACTICE: Safety questions posed at a single timepoint during an MR screening process might not reveal all safety risks. Repetition and rephrasing of screening questions leads to increased detection of safety risks. This could be effectively mitigated by a multi-step screening process. A multi-disciplinary safety committee is efficient at short notice responding to unexpected safety issues.

Markers of cardiovascular risk and their reversibility with acute oxygen therapy in Kyrgyz highlanders with high altitude pulmonary hypertension.

BACKGROUND: High altitude pulmonary hypertension (HAPH), a chronic altitude related illness, is associated with hypoxemia, dyspnea and reduced exercise performance. We evaluated ECG and pulse wave-derived markers of cardiovascular risk in highlanders with HAPH (HAPH+) in comparison to healthy highlanders (HH) and lowlanders (LL) and the effects of hyperoxia. METHODS: We studied 34 HAPH+ and 54 HH at Aksay (3250m), and 34 LL at Bishkek (760m), Kyrgyzstan. Mean pulmonary artery pressure by echocardiography was mean±SD 34±3, 22±5, 16±4mmHg, respectively (p<0.05 all comparisons). During quiet rest, breathing room air or oxygen in randomized order, we measured heart-rate adjusted QT interval (QTc), an ECG-derived marker of increased cardiovascular mortality, and arterial stiffness index (SI), a marker of cardiovascular disease derived from pulse oximetry plethysmograms. RESULTS: Pulse oximetry in HAPH+, HH and LL was, mean±SD, 88±4, 92±2 and 95±2%, respectively (p<0.05 vs HAPH+, both comparisons). QTc in HAPH+, HH and LL was 422±24, 405±27, 400±28ms (p<0.05 HAPH+ vs. others); corresponding SI was 10.5±1.9, 8.4±2.6, 8.5±2.0m/s, heart rate was 75±8, 68±8, 70±10 bpm (p<0.05, corresponding comparisons HAPH+ vs. others). In regression analysis, HAPH+ was an independent predictor of increased QTc and SI when controlled for several confounders. Oxygen breathing increased SI in HH but not in HAPH+, and reduced QTc in all groups. CONCLUSIONS: Our data suggest that HAPH+ but not HH may be at increased risk of cardiovascular mortality and morbidity compared to LL. The lack of a further increase of the elevated SI during hyperoxia in HAPH+ may indicate dysfunctional control of vascular tone and/or remodelling.

High Spatiotemporal Resolution 4D Flow MRI of Intracranial Aneurysms at 7T in 10 Minutes.

BACKGROUND AND PURPOSE: Patients with intracranial aneurysms may benefit from 4D flow MR imaging because the derived wall shear stress is considered a useful marker for risk assessment and growth of aneurysms. However, long scan times limit the clinical implementation of 4D flow MR imaging. Therefore, this study aimed to investigate whether highly accelerated, high resolution, 4D flow MR imaging at 7T provides reliable quantitative blood flow values in intracranial arteries and aneurysms. MATERIALS AND METHODS: We used pseudospiral Cartesian undersampling with compressed sensing reconstruction to achieve high spatiotemporal resolution (0.5 mm isotropic, ∼30 ms) in a scan time of 10 minutes. We analyzed the repeatability of accelerated 4D flow scans and compared flow rates, stroke volume, and the pulsatility index with 2D flow and conventional 4D flow MR imaging in a flow phantom and 15 healthy subjects. Additionally, accelerated 4D flow MR imaging with high spatiotemporal resolution was acquired in 5 patients with aneurysms to derive wall shear stress. RESULTS: Flow-rate bias compared with 2D flow was lower for accelerated than for conventional 4D flow MR imaging (0.31 ± 0.13, P = .22, versus 0.79 ± 0.17 mL/s, P < .01). Pulsatility index bias gave similar results. Stroke volume bias showed no difference for accelerated as well as for conventional 4D flow compared to 2D flow MR imaging. Repeatability for accelerated 4D flow was similar to that of 2D flow MR imaging. Increased temporal resolution for wall shear stress measurements in 5 intracranial aneurysms did not show a consistent effect for the wall shear stress but did show an effect for the oscillatory shear index. CONCLUSIONS: Highly accelerated high spatiotemporal resolution 4D flow MR imaging at 7T in intracranial arteries and aneurysms provides repeatable and accurate quantitative flow values. Flow rate accuracy is significantly increased compared with conventional 4D flow scans.

Early use of alcohol associated with sociodemographic, nutritional and lifestyle factors: survival analysis with Brazilian students.

BACKGROUND: To evaluate the early age of onset (AOO) of alcohol consumption and its association with sociodemographic, nutritional and lifestyle characteristics. METHODS: A national cross-sectional multi-centered study assessed 12-17-year old adolescents from 1247 public and private schools in 124 Brazilian municipalities with more than 100 000 habitants. Our variable of interest was the AOO of alcohol consumption. Covariates comprised sociodemographic status, lifestyle habits and nutritional parameters. We used adapted survival models to investigate the association between covariates and the AOO of alcohol consumption. RESULTS: From a sample of 67 672 adolescents, 50% were females. The mean AOO of alcohol consumption was 12.9 years. Male adolescents had a lower mean age of alcohol experimentation when compared to females in Northeast and South regions. The difference between private and public school for AOO was observed only for the Northeast Region (12.6 versus 13.1, respectively). Adolescents who reported smoking or mental health problems or from the Southern Region presented earlier alcohol use. Physical activity and overweight were positively associated with earlier use of alcohol. CONCLUSIONS: There is no homogeneity in the AOO of alcohol consumption among adolescents, which should be considered when formulating public policies and government campaigns directed toward reducing alcohol consumption.

Uncompromised MRI of knee cartilage while incorporating sensitive sodium MRI.

Sodium imaging is able to assess changes in ion content, linked to glycosaminoglycan content, which is important to guide orthopeadic procedures such as articular cartilage repair. Sodium imaging is ideally performed using double tuned RF coils, to combine high resolution morphological imaging with biochemical information from sodium imaging to assess ion content. The proton image quality of such coils is often harshly degraded, with up to 50% of SNR or severe acceleration loss as compared to single tuned coils. Reasons are that the number of proton receive channels often severely reduced and double tuning will degrade the intrinsic sensitivity of the RF coil on at least one of the nuclei. However, the aim of this work was to implement a double-tuned sodium/proton knee coil setup without deterioration of the proton signal whilst being able to achieve acquisition of high SNR sodium images. A double-tuned knee coil was constructed as a shielded birdcage optimized for sodium and compromised for proton. To exclude any compromise, the proton part of the birdcage is used for transmit only and interfaced to RF amplifiers that can fully mitigate the reduced efficiency. In addition, a 15 channel single tuned proton receiver coil was embedded within the double-resonant birdcage to maintain optimal SNR and acceleration for proton imaging. To validate the efficiency of our coil, the designed coil was compared with the state-of-the-art single-tuned alternative at 7 T. B1+ corrected SNR maps were used to compare both coils on proton performance and g-factor maps were used to compare both coils on acceleration possibilities. The newly constructed double-tuned coil was shown to have comparable proton quality and acceleration possibilities to the single-tuned alternative while also being able to acquire high SNR sodium images.

Aqueductal CSF Stroke Volume Is Increased in Patients with Idiopathic Normal Pressure Hydrocephalus and Decreases after Shunt Surgery.

BACKGROUND AND PURPOSE: Increased CSF stroke volume through the cerebral aqueduct has been proposed as a possible indicator of positive surgical outcome in patients with idiopathic normal pressure hydrocephalus; however, consensus is lacking. In this prospective study, we aimed to compare CSF flow parameters in patients with idiopathic normal pressure hydrocephalus with those in healthy controls and change after shunt surgery and to investigate whether any parameter could predict surgical outcome. MATERIALS AND METHODS: Twenty-one patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched healthy controls were prospectively included and examined clinically and with MR imaging of the brain. Eighteen patients were treated with shunt implantation and were re-examined clinically and with MR imaging the day before the operation and 3 months postoperatively. All MR imaging scans included a phase-contrast sequence. RESULTS: The median aqueductal CSF stroke volume was significantly larger in patients compared with healthy controls (103.5 µL; interquartile range, 69.8-142.8 µL) compared with 62.5 µL (interquartile range, 58.3-73.8 µL; P < .01) and was significantly reduced 3 months after shunt surgery from 94.8 µL (interquartile range, 81-241 µL) to 88 µL (interquartile range, 51.8-173.3 µL; P < .05). Net flow in the caudocranial direction (retrograde) was present in 11/21 patients and in 10/21 controls. Peak flow and net flow did not differ between patients and controls. There were no correlations between any CSF flow parameters and surgical outcomes. CONCLUSIONS: Aqueductal CSF stroke volume was increased in patients with idiopathic normal pressure hydrocephalus and decreased after shunt surgery, whereas retrograde aqueductal net flow did not seem to be specific for patients with idiopathic normal pressure hydrocephalus. On the basis of the results, the usefulness of CSF flow parameters to predict outcome after shunt surgery seem to be limited.

Associations of multiple unhealthy lifestyle behaviors with overweight/obesity and abdominal obesity among Brazilian adolescents: A country-wide survey.

BACKGROUND AND AIMS: Physical inactivity, unhealthy diet, smoking and heavy drinking are four key unhealthy lifestyle behaviors (ULB) that may influence body weight and obesity development. More recently, sedentary time has been recognized as another potentially emerging ULB related to obesity. We therefore investigated the association of multiple ULB with overweight/obesity and abdominal obesity among Brazilian adolescents. METHODS AND RESULTS: This cross-sectional study involved 62,063 students (12-17 years). Physical inactivity, high screen time, low fiber intake, binge drinking and smoking were self-reported and combined to a ULB risk score, ranging from zero to five. Participants were classified as overweight/obese or with abdominal obesity using sex and age-specific cut-off points for BMI and waist circumference, respectively. Poisson regression models were used to examine the associations between ULB with overweight/obesity and abdominal obesity, adjusted for socio-demographic variables. Overall, 2.3%, 18.9%, 43.9%, 32.3% and 2.6% of participants reported zero, one, two, three and four/five ULB, respectively. Higher ULB risk score was associated with overweight/obesity and abdominal obesity in a dose-response gradient. Among 32 possible combinations of ULB, the three most prevalent combinations (physical inactivity + low fiber intake; high screen time + low fiber intake; physical inactivity + high screen time + low fiber intake) were positively associated with general and abdominal obesity. CONCLUSIONS: Our findings suggest a synergistic relationship between ULB and general and abdominal obesity. Preventive efforts targeting combined ULB should be sought to reduce the prevalence of general and abdominal obesity in Brazilian youth.

Update and new insights in encephalitis.

Infectious encephalitis is a rare but severe medical condition resulting from direct invasion of the brain by viruses, bacteria, fungi or parasites, or indirect post-infectious immune or inflammatory disorders when the infectious agent does not cross the blood-brain barrier. Infectious encephalitis cases represent an interesting and accurate sentinel to follow up on trends in infectious diseases or to detect emerging infections. Using Pubmed and Embase, we searched the most relevant publications over the last years. We present here an update on the important findings and new data recently published about infectious encephalitis.

C-reactive protein in Brazilian adolescents: distribution and association with metabolic syndrome in ERICA survey.

BACKGROUND/OBJECTIVES: C-reactive protein (CRP) is a marker of inflammation that has been shown to be predictive of cardiovascular diseases in adults. To evaluate the distribution of CRP as well as its association with metabolic syndrome and its components. SUBJECTS/METHODS: This is a cross-sectional study on adolescents aged 12-17, participants in the Study of Cardiovascular Risk in Adolescents (ERICA). Anthropometric, biochemical and blood pressure data were collected from 6316 adolescents, selected from a random sample of students in the cities of Brasilia, Fortaleza, João Pessoa, Manaus, Porto Alegre and Rio de Janeiro. Metabolic syndrome was defined by the criteria proposed by International Diabetes Federation for adolescent. Poisson regression model with robust variance, taking into consideration the study's complex sampling design, was used to determine multivariate-adjusted prevalence rate ratios expressing the relationship of metabolic syndrome with CRP. RESULTS: In adolescents with metabolic syndrome, CRP concentrations were five times higher (1.01 mg/l; interquartile range (IQR): 0.54-3.47) compared with those without metabolic syndrome (0.19 mg/l; IQR: 0.10-0.78). In multivariate Poisson regression analysis adjusted by sex, age and skin color, the prevalence of elevated CRP (>3.0 mg/l) was almost three times higher in adolescents with metabolic syndrome than in those without this condition (prevalence ratio (PR): 2.9; 95%CI: 2.0-4.3; P<0.001). Of the metabolic syndrome components, elevated waist circumference, low high-density lipoprotein-cholesterol and high triglycerides were significantly related to CRP in a graded (dose-response) manner. CONCLUSIONS: The association of CRP with metabolic syndrome and its components suggests that inflammation may be useful in assessing cardiovascular risk in adolescents.

Does body mass index modify the association between physical activity and screen time with cardiometabolic risk factors in adolescents? Findings from a country-wide survey.

BACKGROUND: Moderate and vigorous physical activity (MVPA) and screen time (ST) have been associated with cardiometabolic health in youth. However, previous studies are conflicting whether these associations are independent of each other and it is unknown if they are modified by adiposity. We aimed to examine the independent and joint associations between MVPA and ST with cardiometabolic risk across body mass index (BMI) categories. METHODS: A total of 36 956 Brazilian adolescents (12-17 years) from the Study of Cardiovascular Risks in Adolescents were included. Information on time spent in MVPA and ST were assessed by self-reports. Blood pressure, Homeostasis Model Assessment of Insulin Resistance, triglycerides, high-density lipoprotein-cholesterol and waist circumference were used to calculate a cardiometabolic risk score (sex-age-specific top-risk quintile for each biomarker). Ordered logistic regression was used to examine the associations. RESULTS: In final adjusted models, both higher MVPA (proportional odds ratio (POR)=0.80; 95% confidence interval (CI): 0.67-0.95) and ST (POR=1.23; 95% CI: 1.10-1.37) were independently associated with cardiometabolic risk. After stratification by normal weight vs overweight/obese, the inverse independent association for MVPA remained unchanged, whereas ST was positively associated with cardiometabolic risk only in overweight/obese adolescents (POR=1.62; 95% CI: 1.18-2.22). Participants who met the recommendations for both MVPA and ST had lower odds for cardiometabolic risk, especially if they were overweight/obese (POR=0.46; 95% CI: 0.31-0.68). CONCLUSIONS: MVPA and ST are independently associated with cardiometabolic risk; the association with ST, however, appears modified by BMI. Normal-weight adolescents should be encouraged to increase MVPA, whereas a combination of increasing MVPA and decreasing ST is recommended in those who are overweight or obese.

Inter-laboratory study of human in vitro toxicogenomics-based tests as alternative methods for evaluating chemical carcinogenicity: a bioinformatics perspective.

The assessment of the carcinogenic potential of chemicals with alternative, human-based in vitro systems has become a major goal of toxicogenomics. The central read-out of these assays is the transcriptome, and while many studies exist that explored the gene expression responses of such systems, reports on robustness and reproducibility, when testing them independently in different laboratories, are still uncommon. Furthermore, there is limited knowledge about variability induced by the data analysis protocols. We have conducted an inter-laboratory study for testing chemical carcinogenicity evaluating two human in vitro assays: hepatoma-derived cells and hTERT-immortalized renal proximal tubule epithelial cells, representing liver and kidney as major target organs. Cellular systems were initially challenged with thirty compounds, genome-wide gene expression was measured with microarrays, and hazard classifiers were built from this training set. Subsequently, each system was independently established in three different laboratories, and gene expression measurements were conducted using anonymized compounds. Data analysis was performed independently by two separate groups applying different protocols for the assessment of inter-laboratory reproducibility and for the prediction of carcinogenic hazard. As a result, both workflows came to very similar conclusions with respect to (1) identification of experimental outliers, (2) overall assessment of robustness and inter-laboratory reproducibility and (3) re-classification of the unknown compounds to the respective toxicity classes. In summary, the developed bioinformatics workflows deliver accurate measures for inter-laboratory comparison studies, and the study can be used as guidance for validation of future carcinogenicity assays in order to implement testing of human in vitro alternatives to animal testing.

Cerebral oxygenation in highlanders with and without high-altitude pulmonary hypertension.

NEW FINDINGS: What is the central question of this study? Cerebral hypoxia impairs cognitive function and exercise performance and may result in brain damage. Residents at high altitude, in particular those with high-altitude pulmonary hypertension, are prone to hypoxaemia due to the exposure to reduced barometric pressure and impaired pulmonary gas exchange. Whether highlanders have a reduced cerebral oxygenation has not been studied. What is the main finding and its importance? We found that despite a reduced arterial oxygen saturation, healthy highlanders and even those with pulmonary hypertension have a similar cerebral oxygenation to healthy lowlanders, suggesting that compensatory mechanisms protect long-term residents at high altitude from cerebral hypoxia. Abstract High-altitude pulmonary hypertension (HAPH), a chronic altitude-related illness, causes hypoxaemia and impaired exercise performance. We evaluated the hypothesis that haemodynamic limitation and hypoxaemia in patients with HAPH are associated with impaired cerebral tissue oxygenation (CTO) compared with healthy highlanders (HH) and lowlanders (LL). We studied 36 highlanders with HAPH and 54 HH at an altitude of 3250 m, and 34 LL at 760 m. Mean(±SD) pulmonary artery pressures were 34(±3), 22(±5) and 16(±4) mmHg, respectively (P < 0.05, all comparisons). The CTO was monitored by near-infrared spectroscopy along with pulse oximetry (peripheral arterial oxygen saturation, SpO2) during quiet breathing of room air (RA) and oxygen for 20 min each, and during hyperventilation with RA and oxygen, respectively. In HAPH, HH and LL breathing RA, SpO2 was 88(±4), 92(±2) and 95(±2)%, respectively (P < 0.001, all comparisons), and CTO was similar in the three groups, at 68(±3), 68(±4) and 69(±4)%, respectively (n.s., all comparisons). Breathing oxygen increased SpO2 and CTO significantly more in HAPH than in HH and LL. Hyperventilation (RA) did not reduce CTO in HAPH but did in HH and LL; hyperventilation (oxygen) increased CTO in HAPH only. Highlanders with and without HAPH studied at 3250 m had a similar CTO to healthy lowlanders at 760 m even though highlanders were hypoxaemic. The physiological response to hyperoxia and hypocapnia assessed by cerebral near-infrared spectroscopy suggests that healthy highlanders and even highlanders with HAPH effectively maintain an adequate CTO. This adaptation may be of particular relevance because adequate cerebral oxygenation is essential for vital brain functions.

Time-varying signal analysis to detect high-altitude periodic breathing in climbers ascending to extreme altitude.

This work investigates the performance of cardiorespiratory analysis detecting periodic breathing (PB) in chest wall recordings in mountaineers climbing to extreme altitude. The breathing patterns of 34 mountaineers were monitored unobtrusively by inductance plethysmography, ECG and pulse oximetry using a portable recorder during climbs at altitudes between 4497 and 7546 m on Mt. Muztagh Ata. The minute ventilation (VE) and heart rate (HR) signals were studied, to identify visually scored PB, applying time-varying spectral, coherence and entropy analysis. In 411 climbing periods, 30-120 min in duration, high values of mean power (MP(VE)) and slope (MSlope(VE)) of the modulation frequency band of VE, accurately identified PB, with an area under the ROC curve of 88 and 89%, respectively. Prolonged stay at altitude was associated with an increase in PB. During PB episodes, higher peak power of ventilatory (MP(VE)) and cardiac (MP(LF)(HR) ) oscillations and cardiorespiratory coherence (MP(LF)(Coher)), but reduced ventilation entropy (SampEn(VE)), was observed. Therefore, the characterization of cardiorespiratory dynamics by the analysis of VE and HR signals accurately identifies PB and effects of altitude acclimatization, providing promising tools for investigating physiologic effects of environmental exposures and diseases.