Unbalanced Response Research Articles

Treatment with <i>Enterococcus faecalis</i> CECT7121 Is Not Effective as Therapy in Mice with an Established Allergy Status

In allergies, an unbalanced immune response towards a T helper (Th) 2 profile with high levels of Immunoglobulin (Ig) E is produced. We have demonstrated that the pre-administration of Enterococcus faecalis CECT7121 prevents the development of allergy in ovalbumin-immunized mice. In this work, we evaluated whether this bacterium can also revert an established allergic status. Mice were immunized with ovalbumin (OVA) and after that, were inoculated with an E. faecalis CECT7121 suspension. In immunized animals, serum specific immune response, proliferative activity of memory splenocytes, and levels of Th2 cytokines were assessed. The in vivo active cutaneous anaphylaxis test was also performed. The treatment with E. faecalis CECT7121 only increased anti-OVA IgG2a levels. No differences were observed in other specific immunological parameters. Probiotic-treatment did not prove to have any desensitizing effect on mice. These results, together with those recently published, can be concluded that this bacterium would not be appropriate for the treatment of allergic symptoms.

Influence of the Radial Clearance of a Squeeze Film Damper on the Vibratory Behavior of a Single Spool Gas Turbine Designed for Unmanned Aerial Vehicle Applications

This study presents a numerical investigation using the finite element method on the vibratory behavior of a single spool gas turbine designed for unmanned aerial vehicle applications. The shaft of the rotor-bearing system is supported on a front bearing composed of a deep groove ball bearing with a vibration absorber element and a rear squeeze film damper bearing. Three radial clearances for the squeeze film damper were analyzed to determine the best geometric configuration for the rear bearing, considering the rotordynamic performance of the entire system. Whirl speeds and unbalanced system responses were carefully evaluated to determine the best radial clearance for the squeeze film damper. After defining the best radial clearance, a transient analysis was performed to simulate the transition of the system through resonance, and a spectral map is presented to illustrate the vibratory behavior of the system considering the influence of all related important frequencies. The rotordynamic behavior of the system is predicted, and vibration problems are avoided. Its mechanical drawings were released to manufacturing, and the first prototype is in the experimental test phase, thus indicating that the numerical results presented in this study are consistent.

The Universal Patient Centeredness Questionnaire: scaling approaches to reduce positive skew.

PurposeSurveys of patients’ experiences typically show results that are indicative of positive experiences. Unbalanced response scales have reduced positive skew for responses to items within the Universal Patient Centeredness Questionnaire (UPC-Q). The objective of this study was to compare the unbalanced response scale with another unbalanced approach to scaling to assess whether the positive skew might be further reduced.Patients and methodsThe UPC-Q was included in a patient experience survey conducted at the ward level at six hospitals in Norway in 2015. The postal survey included two reminders to nonrespondents. For patients in the first month of inclusion, UPC-Q items had standard scaling: poor, fairly good, good, very good, and excellent. For patients in the second month, the scaling was more positive: poor, good, very good, exceptionally good, and excellent. The effect of scaling on UPC-Q scores was tested with independent samples t-tests and multilevel linear regression analysis, the latter controlling for the hierarchical structure of data and known predictors of patient-reported experiences.ResultsThe response rate was 54.6% (n=4,970). Significantly lower scores were found for all items of the more positively worded scale: UPC-Q total score difference was 7.9 (P<0.001), on a scale from 0 to 100 where 100 is the best possible score. Differences between the four items of the UPC-Q ranged from 7.1 (P<0.001) to 10.4 (P<0.001). Multivariate multilevel regression analysis confirmed the difference between the response groups, after controlling for other background variables; UPC-Q total score difference estimate was 8.3 (P<0.001).ConclusionThe more positively worded scaling significantly lowered the mean scores, potentially increasing the sensitivity of the UPC-Q to identify differences over time and between providers. However, none of the groups exhibited large positive skew and ceiling effects, implying that such effects might not be a big measurement problem for either scaling format. We recommend using the standard scaling in surveys producing external indicators for inter-provider comparisons. The more positively worded scaling has greater relevance for local measurement work where the results of patient experience surveys have shown large positive skew, and intra-provider comparison is the primary goal.

A male and female RNA marker to infer sex in forensic analysis

In forensics, DNA profiling is used for the identification of the donor of a trace, while messenger RNA (mRNA) profiling can be applied to identify the cellular origin such as body fluids or organ tissues. The presence of male cell material can be readily assessed by the incorporation of Y-chromosomal markers in quantitation or STR profiling systems. However, no forensic marker exists to positively identify female cell material; merely the presence of female DNA is deduced from the absence of a Y peak, or unbalanced X-Y signals at the Amelogenin locus or unbalanced response of the total and Y-specific quantifier. The presence of two X-chromosomes in female cells invokes dosage compensation, which is achieved through inactivation of one of the X-chromosomes in females. Since this process involves specific RNA molecules, identification of female cellular material may be possible through RNA profiling. Additionally, male material may be identified through RNAs expressed from the Y-chromosome. RNAs preferentially expressed in either sex were assessed for their potential to act as sex markers in forensic RNA assays. To confirm sex-specificity, body fluids and organ tissues of multiple donors of either sex were tested. Additionally, sensitivity of the markers and the suitability of positively identifying male-female mixtures were assessed and degraded samples were used to assess performance of the markers in forensic settings. The addition of sex-specific markers is of added informative value in any RNA profiling system and both markers were incorporated into existing RNA assays that either target body fluids or organs. These are the first forensic assays that enable positive identification of female cellular material.

Strain-dependent response to stimulation in middle-aged rat macrophages: A quest after a useful indicator of healthy aging

Rats of Albino Oxford (AO) strain in our animal facility exhibit a longer average healthy life span than rats of Dark Agouit (DA) strain. Since chronic activation of macrophages contributes to chronic low level inflammation common in older age, elucidation of the changes in middle-aged rats could be useful in prevention of unbalanced inflammatory response in advanced age. We have analysed the phenotype of unelicited and thioglycollate-elicited peritoneal macrophages from young and middle-aged DA and AO rats and tested functions of these cells following stimulation with lipopolysaccharide (LPS) in vitro. Unelicited cells from middle-aged DA rats produced higher amounts of proinflammatory mediators interleukin-6 (IL-6) and nitric oxide (NO), but have a diminished response to LPS stimulation then cells from young rats, in spite of increased frequency of TLR4- and CD14-expressing mature macrophages. Injection of thioglycollate robustly increased overall cytokine production in young rats' macrophages, while diminishing their response to LPS stimulation. In middle-aged DA rats injection of thioglycollate diminished IL-6 production, but increased it in response to LPS stimulation. Quite the contrary to DA rats, the macrophages from middle-aged AO rats have released diminished levels of TNF-α and NO, whereas urea production was strongly increased, when compared to the macrophages from young rats. Although the thioglycollate injection has increased the proportion of CD86+MHCII+ mature macrophages in young rats, and percentages of activated TLR4+ macrophages in both age groups of AO rats, it has not affected the cytokine production in young rats' macrophages, and the TNF-α production in middle-aged rats' macrophages. Moreover, the injection of thioglycollate has robustly increased the production of urea in macrophages derived from both age groups of AO rats. Although middle-aged rats of both strains were healthy during experiment, differences between the inflammatory responses of peritoneal macrophages of middle-aged rats of these strains might be one of the contributing factors defining their health in their advanced age. Development of strategies for the prevention of undesirable inflammatory changes in the elderly would benefit from the prospective study of the middle-aged.

The influence of asymmetry in centralizing spring of squeeze film damper on stability and bifurcation of rigid rotor response

One of the main challenges in the design of rotating machinery is the occurrence of undesirable vibration. In this paper, stability and bifurcation of the unbalance response of a rigid rotor supported by squeeze film damper with asymmetry in centralizing spring are investigated. The unbalanced rotor response is determined by the shooting method and the stability of these solutions is examined by using the Floquet theorem. Numerical examples are given for both symmetric (Kx=Ky) and asymmetry (Kx≠Ky) centralizing springs in x or y direction. Jump phenomenon and subharmonic and quasi-periodic vibrations are predicted for a range of design and operating parameters such as the unbalancing (U), gravity (W), bearing (B) and spring (K). The results show that increasing the spring stiffness asymmetry parameter in y direction has no influence on the nature of system response and occurrence of bifurcation. But, examining the effect of increase in stiffness parameter in x direction leads to occurrence instability and period-doubling bifurcation in response to the system. Our findings show that this phenomena are due to the weight force in the y direction. Finally, it is shown that the unsymmetrical stiffness of squeeze film dampers in the presence of cavitation promoting the chance of undesirable nonsynchronous vibrations.

Human Respiratory Syncytial Virus: Infection and Pathology.

The human respiratory syncytial virus (hRSV) is by far the major cause of acute lower respiratory tract infections (ALRTIs) worldwide in infants and children younger than 2 years. The overwhelming number of hospitalizations due to hRSV-induced ALRTI each year is due, at least in part, to the lack of licensed vaccines against this virus. Thus, hRSV infection is considered a major public health problem and economic burden in most countries. The lung pathology developed in hRSV-infected individuals is characterized by an exacerbated proinflammatory and unbalanced Th2-type immune response. In addition to the adverse effects in airway tissues, hRSV infection can also cause neurologic manifestations in the host, such as seizures and encephalopathy. Although the origins of these extrapulmonary symptoms remain unclear, studies with patients suffering from neurological alterations suggest an involvement of the inflammatory response against hRSV. Furthermore, hRSV has evolved numerous mechanisms to modulate and evade the immune response in the host. Several studies have focused on elucidating the interactions between hRSV virulence factors and the host immune system, to rationally design new vaccines and therapies against this virus. Here, we discuss about the infection, pathology, and immune response triggered by hRSV in the host.

Investigation on an experimental approach to evaluate a wear model for hydrodynamic cylindrical bearings

This work aims to investigate and identify the wear parameters in cylindrical hydrodynamic bearings, an inherent problem due to repeated use of rotating machinery, accentuated in starts/stops or during the crossover of resonance. Thereby, a mathematical model to represent the wear in terms of its main parameters is used, namely, the maximum depth, the angular span and the angular position. The pressure distribution and the hydrodynamic forces generated by the oil film are numerically obtained, properly adapted for discontinuous oil film. The rotor model is represented by finite element method and the bearings are approximated by dynamic coefficients of stiffness and damping. The evaluation and identification of the wear parameters is taken from the unbalanced frequency response of the rotor-bearing system in directional coordinates.

Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease.

Chronic chagasic cardiomyopathy (CCC) progresses with parasite persistence, fibrosis, and electrical alterations associated with an unbalanced immune response such as high plasma levels of tumor necrosis factor (TNF) and nitric oxide (NO). Presently, the available treatments only mitigate the symptoms of CCC. To improve CCC prognosis, we interfered with the parasite load and unbalanced immune response using the trypanocidal drug benznidazole (Bz) and the immunoregulator pentoxifylline (PTX). C57BL/6 mice chronically infected with the Colombian strain of Trypanosoma cruzi and with signs of CCC were treated for 30 days with a suboptimal dose of Bz (25 mg/kg of body weight), PTX (20 mg/kg), or their combination (Bz plus PTX) and analyzed for electrocardiographic, histopathological, and immunological changes. Bz (76%) and Bz-plus-PTX (79%) therapies decreased parasite loads. Although the three therapies reduced myocarditis and fibrosis and ameliorated electrical alterations, only Bz plus PTX restored normal heart rate-corrected QT (QTc) intervals. Bz-plus-PTX-treated mice presented complementary effects of Bz and PTX, which reduced TNF expression (37%) in heart tissue and restored normal TNF receptor 1 expression on CD8+ T cells, respectively. Bz (85%) and PTX (70%) therapies reduced the expression of inducible nitric oxide synthase (iNOS/NOS2) in heart tissue, but only Bz (58%) reduced NO levels in serum. These effects were more pronounced after Bz-plus-PTX therapy. Moreover, 30 to 50 days after treatment cessation, reductions of the prolonged QTc and QRS intervals were sustained in Bz-plus-PTX-treated mice. Our findings support the importance of interfering with the etiological agent and immunological abnormalities to improve CCC prognosis, opening an opportunity for a better quality of life for Chagas' disease (CD) patients.

Serglycin proteoglycans limit enteropathy in Trichinella spiralis-infected mice.

BackgroundSerglycin proteoglycans are essential for maturation of secretory granules and for the correct granular storage of cationic proteases in hematopoietic cells, e.g. mast cells. However, little is known about the in vivo functions of serglycin proteoglycans during infection. Here we investigated the potential role of serglycin proteoglycans in host defense after infection with the nematode Trichinella spiralis.ResultsTwelve days post infection lack of serglycin proteoglycans caused significantly increased enteropathy. The serglycin-deficient mice showed significantly increased intestinal worm burden, reduced recruitment of mast cells to the intestinal crypts, decreased levels of the mast cell proteases MCPT5 and MCPT6 in intestinal tissue, decreased serum levels of TNF-α, IL-1β, IL-10 and IL-13, increased levels of IL-4 and total IgE in serum, and increased intestinal levels of the neutrophil markers myeloperoxidase and elastase, as compared to wild type mice. At five weeks post infection, increased larvae burden and inflammation were seen in the muscle tissue of the serglycin-deficient mice.ConclusionsOur results demonstrate that the serglycin-deficient mice were more susceptible to T. spiralis infection and displayed an unbalanced immune response compared to wild type mice. These findings point to an essential regulatory role of serglycin proteoglycans in immunity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-016-0155-y) contains supplementary material, which is available to authorized users.

The Universal Patient Centeredness Questionnaire: reliability and validity of a one-page questionnaire following surveys in three patient populations.

BackgroundThis study developed and tested the reliability and validity of the Universal Patient Centeredness Questionnaire (UPC-Q).MethodsThe UPC-Q developed in this study has three parts: 1) the aspects that patients consider the most important when receiving a relevant health care service, rating the health care services on these aspects and their prioritization, 2) the overall experiences of patients using the relevant health care service, and 3) suggestions for improvements. The UPC-Q was tested in four different patient-experience surveys in 2015, including psychiatric inpatients (n=109), general practitioner (GP) patients (n=1,059), and inpatients from two hospital samples (n=973, n=599). The UPC-Q was tested for item completeness and ceiling effects, while the UPC-Q scale consisting of the first part of the UPC-Q was tested for internal consistency reliability and construct validity.ResultsThe percentage of patients rating at least one aspect was 70.6% for psychiatric inpatients, 77.6% for hospital inpatients, and 90.6% for GP patients, while 88.9% of the psychiatric inpatients, 93.1% of the hospital inpatients, and 95.3% of the GP patients were able to prioritize the aspects. The internal consistency reliability of the UPC-Q scale was acceptable in all samples (Cronbach’s alpha >0.7), and construct validity was supported by 20 of 21 significant associations between the UPC-Q and related variables. The UPC-Q total score was skewed toward positive evaluations, but the ceiling effect was smaller for an unbalanced response scale than for a balanced scale.ConclusionThe UPC-Q includes ratings of what is most important for individual patients, while at the same time providing data for improving the quality of health care and making it possible to monitor trends within and across patient populations. This study included psychiatric inpatients, hospital inpatients, and GP patients, and found that the UPC-Q performed well in terms of acceptance, internal consistency reliability, and construct validity.

Primary dengue haemorrhagic fever in patients from northeast of Brazil is associated with high levels of interferon-β during acute phase.

Dengue is an acute febrile disease caused by the mosquito-borne dengue virus (DENV) that according to clinical manifestations can be classified as asymptomatic, mild or severe dengue. Severe dengue cases have been associated with an unbalanced immune response characterised by an over secretion of inflammatory cytokines. In the present study we measured type I interferon (IFN-I) transcript and circulating levels in primary and secondary DENV infected patients. We observed that dengue fever (DF) and dengue haemorrhagic fever (DHF) patients express IFN-I differently. While DF and DHF patients express interferon-α similarly (52,71 ± 7,40 and 49,05 ± 7,70, respectively), IFN- β were associated with primary DHF patients. On the other hand, secondary DHF patients were not able to secrete large amounts of IFN- β which in turn may have influenced the high-level of viraemia. Our results suggest that, in patients from our cohort, infection by DENV serotype 3 elicits an innate response characterised by higher levels of IFN- β in the DHF patients with primary infection, which could contribute to control infection evidenced by the low-level of viraemia in these patients. The present findings may contribute to shed light in the role of innate immune response in dengue pathogenesis.

West African monsoon dynamics and precipitation: the competition between global SST warming and CO2 increase in CMIP5 idealized simulations

Climate variability associated with the West African monsoon (WAM) has important environmental and socio-economic impacts in the region. However, state-of-the-art climate models still struggle in producing reliable climate predictions. An important cause of this low predictive skill is the sensitivity of climate models to different forcings. In this study, the mechanisms linking the WAM dynamics to the CO2 forcing are investigated, by comparing the effect of the CO2 direct radiative effect with its indirect effect mediated by the global sea surface warming. The July-to-September WAM variability is studied in climate simulations extracted from the Coupled Model Intercomparison Project Phase 5 archive, driven by prescribed sea surface temperature (SST). The individual roles of global SST warming and CO2 atmospheric concentration increase are investigated through idealized experiments simulating a 4 K warmer SST and a quadrupled CO2 concentration, respectively. Results show opposite and competing responses in the WAM dynamics and precipitation. A dry response (−0.6 mm/day) to the SST warming is simulated in the Sahel, with dryer conditions over western Sahel (−0.8 mm/day). Conversely, the CO2 increase produces wet conditions (+0.5 mm/day) in the Sahel, with the strongest response over central-eastern Sahel (+0.7 mm/day). The associated responses in the atmospheric dynamics are also analysed, showing that the SST warming affects the Sahelian precipitation through modifications in the global tropical atmospheric dynamics, reducing the importance of the regional drivers, while the CO2 increase reinforces the coupling between precipitation and regional dynamics. A general agreement in model responses demonstrates the robustness of the identified mechanisms linking the WAM dynamics to the CO2 direct and indirect forcing, and indicates that these primary mechanisms are captured by climate models. Results also suggest that the spread in future projections may be caused by unbalanced model responses to the CO2 direct and indirect forcing.

Influence of cross-coupling stiffness in tilting pad journal bearings for vertical machines

This paper evaluates how cross-coupling coefficients affects the dynamics of a vertical rotor with tilting pad journal bearings. For vertical machines, the bearing properties are dependent on the bearing load and direction. As a result, it generally requires that bearing properties are calculated at each time step using the governing fluid dynamic equations. This method gives a good representation of the bearing but computational time increases and can cause stability problems. In this study the bearing properties are instead modelled as a function of eccentricity and its direction. Hence, the bearing properties can be evaluated at each time step without solving Navier–Stokes or Reynold׳s equation. The main advantage of using this method is to decrease the computational time. The cross-coupling stiffness and damping coefficients are usually neglected since they are small compared to the radial stiffness and damping coefficients. In this paper, the simulated unbalanced response is compared to experimental results and it is seen that the cross-coupling stiffness for vertical machines can influence the dynamics. It is shown that the cross-coupling can be of the same order of magnitude as the radial stiffness component depending on the shaft angular position in the bearing. Including cross-coupling increases higher frequency components and the experiments show similar behaviour. Hence the cross-coupling stiffness and damping coefficients should be included when simulating vertical machines subjected to high loads or when the detailed dynamical behaviour is important to investigate.

What goes around comes around: novel pharmacological targets in the gut-brain axis.

The gut and the brain communicate bidirectionally through anatomic and humoral pathways, establishing what is known as the gut-brain axis. Therefore, interventions affecting one system will impact on the other, giving the opportunity to investigate and develop future therapeutic strategies that target both systems. Alterations in the gut-brain axis may arise as a consequence of changes in microbiota composition (dysbiosis), modifications in intestinal barrier function, impairment of enteric nervous system, unbalanced local immune response and exaggerated responses to stress, to mention a few. In this review we analyze and discuss several novel pharmacological targets within the gut-brain axis, with potential applications to improve intestinal and mental health.

Nonlinear Frequencies and Unbalanced Response Analysis of High Speed Rotor-Bearing Systems

This paper describes a step forward in calculating the nonlinear frequencies and resultant dynamic behavior of high speed rotor bearing system with mass unbalance. Nonlinear strongly coupled equations of motion has been formulated based on strain energy and kinetic energy equations for shaft, disk and unbalance mass with shaft undergoing large bending deformations. Here gyroscopic effects of disk as well as mass unbalance are also considered while vibration effect along the shaft axis is ignored. Time history and FFT analysis for finding the fundamental frequencies for the rotating are portrayed under variation of shaft diameter, frequency of the shaft speed, geometric nonlinearity and disk location. The present research shows an interesting development that the initial conditions are playing an important role in finding the nonlinear frequencies and this variation is strongly due to the presence of nonlinear geometric coupling. In addition, response analysis of the system has been developed due to mass unbalanced using time history. This paper enables an understanding and realization of operating zones of rotational speed of the shaft by which the excessive vibration can easily be avoided due to the resonant conditions occurred as the natural frequencies come closer to the frequency of the rotational speed.

시스템 식별을 통한 자기베어링 장착 터보 압축기의 불평형 응답 예측

회전 기계에서 회전에 따른 진동은 성능 저하 및 고장의 직접적 원인이 되어, 진동을 예측하고 저감 방안을 수립하는 것이 매우 중요하지만, 회전 기계의 조립이나 설치 과정에서 발생하는 불평형의 변화나 지지 구조물의 진동 모드는 예측이 어려워 그 영향을 사전에 평가하기 어렵다. 본 논문에서는 자기베어링에 의해 지지된 터보 압축기의 전달함수를 시스템 식별과정을 통해 구하고 이를 활용하여 압축기의 불평형 응답을 예측한다. 식별된 전달함수는 회전체의 진동 모드와 지지 구조물의 진동 모드를 함께 포함하고 있어, 불평형 응답에 대한 지지 구조물의 영향을 실질적으로 평가할 수 있다. 저속 운전에 의해 불평형을 추정하고 정격 속도까지의 불평형 응답을 시험 결과와 비교하여 예측의 적절성과 문제점을 파악하였다.

Does More Balanced Survey Response Imply Less Non-Response Bias?

SummaryRecently, various indicators have been proposed as indirect measures of non-response error in surveys. They employ auxiliary variables, external to the survey, to detect non-representative or unbalanced response. A class of designs known as adaptive survey designs maximizes these indicators by applying different treatments to different subgroups. The natural question is whether the decrease in non-response bias that is caused by adaptive survey designs could also be achieved by non-response adjustment methods. We discuss this question and provide theoretical and empirical considerations, supported by a range of household and business surveys. We find evidence that more balanced response coincides with less non-response bias, even after adjustment.

Cardiovascular Response to Chronic Administration of C-type Natriuretic Peptide in Spontaneously Hypertensive Rats

Background: C-type natriuretic peptide (CNP) plays an important role in the regulation of cardiovascular function and morphology.We have previously demonstrated that CNP increases nitric oxide (NO) system activity in vivo in spontaneouslyhypertensive rats (SHR).Objective: The goal of this study is to evaluate the effect of chronic CNP administration on systolic blood pressure (SBP),cardiovascular function and the NO system in spontaneously hypertensive and normotensive rats.Methods: Twelve-week-old normotensive male Wistar rats and SHR were used. They received chronic infusion of saline orCNP (0.75 mg/h/rat) for 14 days via subcutaneously implanted osmotic pumps. Systolic blood pressure was measured and anelectrocardiogram and echocardiogram were performed. The left ventricle and the thoracic aorta were resected; nitric oxidesynthase (NOS) activity was determined using L-[U14C]-arginine and vascular reactivity was assessed.Results: Chronic administration of CNP decreased SBP in SHR. Cardiac output was lower in SHR and increased with CNP;however, CNP had no effect in normotensive rats. Spontaneously hypertensive rats had unbalanced aortic vasodilation andvasoconstriction responses, and CNP improved the vascular function. Nitric oxide synthase activity was greater in SHR andincreased with the 14-day CNP infusion, but this increase was lower than in normotensive rats.Conclusion: C-type natriuretic peptide induces cardiovascular and NO system changes which may be beneficial in this modelof hypertension.

Evaluation of T-wave alternans activity under stress conditions after 5 d and 21 d of sedentary head-down bed rest

It is well known that prolonged microgravity leads to cardiovascular deconditioning, inducing significant changes in autonomic control of the cardiovascular system. This may adversely influence cardiac repolarization, and provoke cardiac rhythm disturbances. T-wave alternans (TWA), reflecting temporal and spatial repolarization heterogeneity, could be affected. The aim of this work was to test the hypothesis that 5 d and 21 d head-down (−6°) bed rest (HDBR) increases TWA, thus suggesting a higher underlying electrical instability and related arrhythmogenic risk.Forty-four healthy male volunteers were enrolled in the experiments as part of the European Space Agency’s HDBR studies. High-fidelity ECG was recorded during orthostatic tolerance (OT) and aerobic power (AP) tests, before (PRE) and after HDBR (POST). A multilead scheme for TWA amplitude estimation was used, where non-normalized and T-wave amplitude normalized TWA indices were computed. In addition, spectral analysis of heart rate variability during OT was assessed.Both 5 d and 21 d HDBR induced a reduction in orthostatic tolerance time (OTT), as well as a decrease in maximal oxygen uptake and reserve capacity, thus suggesting cardiovascular deconditioning. However, TWA indices were found not to increase. Interestingly, subjects with lower OTT after 5 d HDBR also showed higher TWA during recovery after OT testing, associated with unbalanced sympathovagal response, even before the HDBR. In contrast with previous observations, augmented ventricular heterogeneity related to 5 d and 21 d HDBR was not sufficient to increase TWA under stress conditions.