Is a verification phase useful for confirming maximal oxygen uptake in apparently healthy adults? A systematic review and meta-analysis

BackgroundThe 'verification phase' has emerged as a supplementary procedure to traditional maximal oxygen uptake (VO2max) criteria to confirm that the highest possible VO2 has been attained during a cardiopulmonary exercise test (CPET).ObjectiveTo compare the highest VO2 responses observed in different verification phase procedures with their preceding CPET for confirmation that VO2max was likely attained.MethodsMEDLINE (accessed through PubMed), Web of Science, SPORTDiscus, and Cochrane (accessed through Wiley) were searched for relevant studies that involved apparently healthy adults, VO2max determination by indirect calorimetry, and a CPET on a cycle ergometer or treadmill that incorporated an appended verification phase. RevMan 5.3 software was used to analyze the pooled effect of the CPET and verification phase on the highest mean VO2. Meta-analysis effect size calculations incorporated random-effects assumptions due to the diversity of experimental protocols employed. I2 was calculated to determine the heterogeneity of VO2 responses, and a funnel plot was used to check the risk of bias, within the mean VO2 responses from the primary studies. Subgroup analyses were used to test the moderator effects of sex, cardiorespiratory fitness, exercise modality, CPET protocol, and verification phase protocol.ResultsEighty studies were included in the systematic review (total sample of 1,680 participants; 473 women; age 19-68 yr.; VO2max 3.3 ± 1.4 L/min or 46.9 ± 12.1 mL·kg-1·min-1). The highest mean VO2 values attained in the CPET and verification phase were similar in the 54 studies that were meta-analyzed (mean difference = 0.03 [95% CI = -0.01 to 0.06] L/min, P = 0.15). Furthermore, the difference between the CPET and verification phase was not affected by any of the potential moderators such as verification phase intensity (P = 0.11), type of recovery utilized (P = 0.36), VO2max verification criterion adoption (P = 0.29), same or alternate day verification procedure (P = 0.21), verification-phase duration (P = 0.35), or even according to sex, cardiorespiratory fitness level, exercise modality, and CPET protocol (P = 0.18 to P = 0.71). The funnel plot indicated that there was no significant publication bias.ConclusionsThe verification phase seems a robust procedure to confirm that the highest possible VO2 has been attained during a ramp or continuous step-incremented CPET. However, given the high concordance between the highest mean VO2 achieved in the CPET and verification phase, findings from the current study would question its necessity in all testing circumstances.Prospero registration idCRD42019123540

Acute effects of mixed circuit training on hemodynamic and cardiac autonomic control in chronic hemiparetic stroke patients: a randomized controlled crossover trial

Objectives: To investigate whether a single bout of mixed circuit training (MCT) can elicit acute blood pressure (BP) reduction in chronic hemiparetic stroke patients, a phenomenon also known as post-exercise hypotension (PEH). Methods: Seven participants (58 ± 12 years) performed a non-exercise control session (CTL) and a single bout of MCT on separate days and in a randomized counterbalanced order. The MCT included 10 exercises with 3 sets of 15-repetition maximum per exercise, with each set interspersed with 45 s of walking. Systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP), cardiac output (Q), systemic vascular resistance (SVR), baroreflex sensitivity (BRS), and heart rate variability (HRV) were assessed 10 min before and 40 min after CTL and MCT. BP and HRV were also measured during an ambulatory 24-h recovery period. Results: Compared to CTL, SBP (∆-22%), DBP (∆-28%), SVR (∆-43%), BRS (∆-63%), and parasympathetic activity (HF; high-frequency component: ∆-63%) were reduced during 40 min post-MCT (p < 0.05), while Q (∆35%), sympathetic activity (LF; low-frequency component: ∆139%) and sympathovagal balance (LF:HF ratio: ∆145%) were higher (p < 0.001). In the first 10 h of ambulatory assessment, SBP (∆-7%), MAP (∆-6%), and HF (∆-26%) remained lowered, and LF (∆11%) and LF:HF ratio (∆13%) remained elevated post-MCT vs. CTL (p < 0.05). Conclusion: A single bout of MCT elicited prolonged PEH in chronic hemiparetic stroke patients. This occurred concurrently with increased sympathovagal balance and lowered SVR, suggesting vasodilation capacity is a major determinant of PEH in these patients. This clinical trial was registered in the Brazilian Clinical Trials Registry (RBR-5dn5zd), available at https://ensaiosclinicos.gov.br/rg/RBR-5dn5zd. Clinical Trial Registration: https://ensaiosclinicos.gov.br/rg/RBR-5dn5zd, identifier RBR-5dn5z

Confirming the attainment of maximal oxygen uptake within special and clinical groups: a systematic review and meta-analysis of cardiopulmonary exercise test and verification phase protocols

Background and aim A plateau in oxygen uptake (V̇O2) during an incremental cardiopulmonary exercise test (CPET) to volitional exhaustion appears less likely to occur in special and clinical populations. Secondary maximal oxygen uptake (V̇O2max) criteria have been shown to commonly underestimate the actual V̇O2max. The verification phase protocol might determine the occurrence of ‘true’ V̇O2max in these populations. The primary aim of the current study was to systematically review and provide a meta-analysis on the suitability of the verification phase for confirming ‘true’ V̇O2max in special and clinical groups. Secondary aims were to explore the applicability of the verification phase according to specific participant characteristics and investigate which test protocols and procedures minimise the differences between the highest V̇O2 values attained in the CPET and verification phase. Methods Electronic databases (PubMed, Web of Science, SPORTDiscus, Scopus, and EMBASE) were searched using specific search strategies and relevant data were extracted from primary studies. Studies meeting inclusion criteria were systematically reviewed. Meta-analysis techniques were applied to quantify weighted mean differences (standard deviations) in peak V̇O2 from a CPET and a verification phase within study groups using random-effects models. Subgroup analyses investigated the differences in V̇O2max according to individual characteristics and test protocols. The methodological quality of the included primary studies was assessed using a modified Downs and Black checklist to obtain a level of evidence. Participant-level V̇O2 data were analysed according to the threshold criteria reported by the studies or the inherent measurement error of the metabolic analysers and displayed as Bland-Altman plots. 3 Results Forty-three studies were included in the systematic review, whilst 30 presented quantitative information for meta-analysis. Within the 30 studies, the highest mean V̇O2 values attained in the CPET and verification phase protocols were similar (mean difference = -0.00 [95% confidence intervals, CI = -0.03 to 0.03] L·min-1 , p = 0.87; level of evidence, LoE: strong). The specific clinical groups with sufficient primary studies to be meta-analysed showed a similar V̇O2max between the CPET and verification phase (p &gt; 0.05, LoE: limited to strong). Across all 30 studies, V̇O2max was not affected by differences in test protocols (p &gt; 0.05; LoE: moderate to strong). Only 23 (53.5%) of the 43 reviewed studies reported how many participants achieved a lower, equal, or higher V̇O2 value in the verification phase versus the CPET or reported or supplied participant-level V̇O2 data for this information to be obtained. The percentage of participants that achieved a lower, equal, or higher V̇O2 value in the verification phase was highly variable across studies (e.g. the percentage that achieved a higher V̇O2 in the verification phase ranged from 0% to 88.9%). Conclusion Group-level verification phase data appear useful for confirming a specific CPET protocol likely elicited V̇O2max, or a reproducible V̇O2peak, for a given special or clinical group. Participant-level data might be useful for confirming whether specific participants have likely elicited V̇O2max, or a reproducible V̇O2peak, however, more research reporting participant-level data is required before evidence-based guidelines can be given

Whales as marine ecosystem engineers

Baleen and sperm whales, known collectively as the great whales, include the largest animals in the history of life on Earth. With high metabolic demands and large populations, whales probably had a strong influence on marine ecosystems before the advent of industrial whaling: as consumers of fish and invertebrates; as prey to other large-bodied predators; as reservoirs of and vertical and horizontal vectors for nutrients; and as detrital sources of energy and habitat in the deep sea. The decline in great whale numbers, estimated to be at least 66% and perhaps as high as 90%, has likely altered the structure and function of the oceans, but recovery is possible and in many cases is already underway. Future changes in the structure and function of the world\u27s oceans can be expected with the restoration of great whale populations

Chromosome evolution in lophyohylini (amphibia, anura, hylinae)

The hyline tribe Lophyohylini includes 87 species of treefrogs, of which cytogenetics aspects have been studied in less than 20% of them. In order to evaluate the evolution of some of its chromosome characters (NOR position, C-bands, and DAPI/CMA3 bands), we studied the karyotypes of 21 lophyohylines, 16 of them for the first time, and analyzed them in a phylogenetic context. Most species showed similar karyotypes regarding chromosome number (2n = 24) and morphology (FN = 48), excepting Phyllodytes edelmoi and Osteocephalus buckleyi with 2n = 22 (FN = 44) and 2n = 28 (FN = 50), respectively. The NOR location was variable among species and provided valuable phylogenetic information. This marker was located in pair 11 in all species of Trachycephalus, Itapotihyla langsdorffii, and Nyctimantis arapapa, representing the plesiomorphic condition of Lophyohylini. Besides, other apomorphic states were recovered for the clades comprising N. rugiceps and N. siemersi (NOR in pair 5), and Dryaderces pearsoni, Osteocephalus, and Osteopilus (NOR in pair 9). Phyllodytes presented variation for NORs position; they were in pair 2 in P. edelmoi, pair 7 in P. melanomystax, and pair 8 in P. gyrinaethes and P. praeceptor. Polymorphisms in size, number, and activity of this marker were observed for N. siemersi, Osteocephalus fuscifacies, and some species of Trachycephalus. Remarkably, in N. siemersi NORs were detected on a single chromosome in the two specimens studied by this technique, raising the question of how this complex polymorphism is maintained. Interstitial telomeric sequences were found in P. edelmoi,P. melanomystax, and Osteocephalus buckleyi, and their presence seems to be not related to the chromosome reorganization events. Finally, some species showed spontaneous rearrangements, possibly as a consequence of an uncommon phenomenon in anuran cytogenetics: the presence of fragile sites or secondary constrictions not associated with NORs. We propose that this rare feature would have played an important role in the evolution of this group of frogs. From the evidence obtained in this and previous studies, we conclude that Lophyohylini presents a complex chromosome evolution.Fil: Suarez, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Ferro, Juan Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Nagamachi, Cleusa Y.. Universidade Federal do Pará; BrasilFil: Cardozo, Dario Elbio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Blasco zuñiga, Ailin. Pontificia Universidad Católica del Ecuador; EcuadorFil: Silva, Jéssica B.. Universidade Federal do Pará; BrasilFil: Marciano Jr, Euvaldo. Universidade Estadual de Santa Cruz; BrasilFil: Costa, Marco A.. Universidade Estadual de Santa Cruz; BrasilFil: Orrico, Victor G.D.. Universidade Estadual de Santa Cruz; BrasilFil: Solé, Mirco. Universidade Estadual de Santa Cruz; BrasilFil: Roberto, Igor J.. Universidad Federal del Amazonas.; BrasilFil: Rivera, Miryan. Pontificia Universidad Católica del Ecuador; EcuadorFil: Wiley, John E.. University School of Medicine; Estados UnidosFil: Faivovich, Julián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Baldo, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Pieczarka, Julio. Universidade Federal do Pará; Brasi

A Cautionary Tale: MARVELS Brown Dwarf Candidate Reveals Itself To Be A Very Long Period, Highly Eccentric Spectroscopic Stellar Binary

We report the discovery of a highly eccentric, double-lined spectroscopic binary star system (TYC 3010-1494-1), comprising two solar-type stars that we had initially identified as a single star with a brown dwarf companion. At the moderate resolving power of the MARVELS spectrograph and the spectrographs used for subsequent radial-velocity (RV) measurements (R ~ <30,000), this particular stellar binary mimics a single-lined binary with an RV signal that would be induced by a brown dwarf companion (Msin(i)~50 M_Jup) to a solar-type primary. At least three properties of this system allow it to masquerade as a single star with a very low-mass companion: its large eccentricity (e~0.8), its relatively long period (P~238 days), and the approximately perpendicular orientation of the semi-major axis with respect to the line of sight (omega~189 degrees). As a result of these properties, for ~95% of the orbit the two sets of stellar spectral lines are completely blended, and the RV measurements based on centroiding on the apparently single-lined spectrum is very well fit by an orbit solution indicative of a brown dwarf companion on a more circular orbit (e~0.3). Only during the ~5% of the orbit near periastron passage does the true, double-lined nature and large RV amplitude of ~15 km/s reveal itself. The discovery of this binary system is an important lesson for RV surveys searching for substellar companions; at a given resolution and observing cadence, a survey will be susceptible to these kinds of astrophysical false positives for a range of orbital parameters. Finally, for surveys like MARVELS that lack the resolution for a useful line bisector analysis, it is imperative to monitor the peak of the cross-correlation function for suspicious changes in width or shape, so that such false positives can be flagged during the candidate vetting process.Comment: 16 pages, 11 figures, 6 table

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

First glimpse of the soft x-ray induced excited spin-state trapping effect dynamics on spin cross-over molecules

The dynamics of the soft x-ray induced excited spin state trapping (SOXIESST) effect of Fe(phen)(2)(NCS)(2) (Fe-phen) powder have been investigated by x-ray absorption spectroscopy (XAS) using the total electron yield method, in a wide temperature range. The low-spin (LS) state is excited into the metastable high-spin (HS) state at a rate that depends on the intensity of the x-ray illumination it receives, and both the temperature and the intensity of the x-ray illumination will affect the maximum HS proportion that is reached. We find that the SOXIESST HS spin state transforms back to the LS state at a rate that is similar to that found for the light induced excited spin state trapping (LIESST) effect. We show that it is possible to use the SOXIESST effect in combination with the LIESST effect to investigate the influence of cooperative behavior on the dynamics of both effects. To investigate the impact of molecular cooperativity, we compare our results on Fe-phen with those obtained for Fe[Me(2)Pyrz](3)BH(2) (Fe-pyrz) powder, which exhibits a similar thermal transition temperature but with a hysteresis. We find that, while the time constant of the dynamic is identical for both molecules, the SOXIESST effect is less efficient at exciting the HS state in Fe-pyrz than in Fe-phen. (C) 2013 AIP Publishing LLC