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Key Clinical Message In chronic heart failure, dilutional anemia and hypervolemia may occur due to plasma volume expansion, the latter sometimes exacerbated by an increase in red cell volume. Diagnosis and a therapeutic strategy require determination of vascular volumes.

El artículo indaga sobre el pensamiento matemático manifestado por estudiantes de quinto grado, cuando inventan y resuelven problemas matemáticos. El problema de investigación refiere al desconocimiento del pensamiento matemático de los estudiantes y cómo se suele infravalorar cuando se hace mediante pruebas estandarizadas. Conocer el pensamiento matemático de los estudiantes ayuda a construir procesos de estudio que los reconozca. La investigación se realizó durante un año, es cualitativa y naturalista, se utilizó la invención y solución de problemas para determinar tanto el pensamiento matemático de los estudiantes como estrategias de solución. Los registros se tomaron de la producción escrita de cuarenta niños de quinto grado, cuando inventaron problemas para ser propuestos y resueltos por sus compañeros. Los resultados informan que los niños inventan problemas de naturaleza aritmética, prefieren las operaciones entre números sobre las relaciones entre ellos, y manifiestan dificultades para proponer problemas cuando se les da información.

Receptor protein tyrosine phosphatases γ and ζ (RPTPγ and RPTPζ) are transmembrane signaling proteins with extracellular carbonic anhydrase–like domains that play vital roles in the development and functioning of the central nervous system (CNS) and are implicated in tumor suppression, neurodegeneration, and sensing of extracellular [CO2] and [HCO3−]. RPTPγ expresses throughout the body, whereas RPTPζ preferentially expresses in the CNS. Here, we investigate differential RPTPγ-RPTPζ expression in three sources derived from a wild-type laboratory strain of C57BL/6 mice: (a) mixed neuron–astrocyte hippocampal (HC) cultures 14 days post isolation from P0–P2 pups; (b) P0–P2 pup hippocampi; and (c) 9- to 12-week-old adult hippocampi. Regarding RPTPγ, we detect the Ptprg variant-1 (V1) transcript, representing canonical exons 1–30. Moreover, we newly validate the hypothetical assembly [XM_006517956] (propose name, Ptprg-V3), which lacks exon 14. Both transcripts are in all three HC sources. Regarding RPTPζ, we confirm the expression of Ptprz1-V1, detecting it in pups and adults but not in cultures, and Ptprz1-V3 through Ptprz1-V7 in all three preparations. We newly validate hypothetical assemblies Ptprz1-X1 (in cultures and pups), Ptprz1-X2 (in all three), and Ptprz1-X5 (in pups and adults) and propose to re-designate them as Ptprz1-V0, Ptprz1-V2, and Ptprz1-V8, respectively. The diversity of RPTPγ and RPTPζ splice variants likely corresponds to distinct signaling functions, in different cellular compartments, during development vs later life. In contrast to previous studies that report divergent RPTPγ and RPTPζ protein expressions in neurons and sometimes in the glia, we observe that RPTPγ and RPTPζ co-express in the somata and processes of almost all HC neurons but not in astrocytes, in all three HC preparations.

Abstract The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity and tissue function with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5 + ) in their native in vivo state, we find an expanded pool of Lgr5 + cells in NMRs, and these cells specifically at the crypt base (Lgr5 +CBC ) exhibit slower division rates compared to those in short-lived mice but have a similar turnover as human LGR5 +CBC cells. Instead of entering quiescence (G0), NMR Lgr5 +CBC cells reduce their division rates by prolonging arrest in the G1 and/or G2 phases of the cell cycle. Moreover, we also observe a higher proportion of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust pro-apoptotic, anti-proliferative response within the stem/progenitor cell zone.

Introducción: La revisión en dos tiempos se considera el método de referencia para tratar a pacientes con artroplastia de cadera e infección crónica. Sin embargo, durante el retiro de un vástago femoral no cementado fijo, se puede dañar el fémur proximal, lo que puede plantear dificultades en el reimplante. Objetivo: Determinar si la infección periprotésica crónica de cadera se puede tratar con un intercambio parcial de sus componentes, conservando un vástago femoral no cementado fijo. Materiales y Métodos: Estudio de serie de casos retrospectivo, multicéntrico que incluyó a 9 pacientes con artroplastia de cadera e infección crónica, programados para el recambio parcial en uno o dos tiempos con retención del tallo femoral fijo, entre enero de 2014 y noviembre de 2019. Se evaluó la evolución mediante el examen clínico, el puntaje de cadera de Harris, y estudios de laboratorio y radiológicos. Resultados: En un seguimiento medio de 5.8 años de 9 pacientes con artroplastia de cadera no cementada, después del reimplante de la prótesis, la infección remitió en 8 pacientes (88,9%), y el puntaje medio de cadera de Harris fue de 81 en el último control. No hubo aflojamiento de componentes acetabulares ni femorales. Conclusiones: La conservación de vástagos femorales no cementados puede representar una opción aceptable para los pacientes con infección periprotésica crónica de cadera cuando la extracción del componente femoral daría como resultado una pérdida significativa de hueso y un compromiso de la reconstrucción. Sin embargo, se requieren más estudios sobre esta técnica.

Several technological approaches have been used to develop vaccines against COVID-19, including those based on inactivated viruses, viral vectors, and mRNA. This study aimed to monitor the maintenance of anti-SARS-CoV-2 antibodies in individuals from Brazil according to the primary vaccination regimen, as follows: BNT162b2 (group 1; 22) and ChAdOx1 (group 2; 18). Everyone received BNT162b2 in the first booster while in the second booster CoronaVac, Ad26.COV2.S, or BNT162b2. Blood samples were collected from 2021 to 2023 to analyze specific RBD (ELISA) and neutralizing antibodies (PRNT50). We observed a progressive increase in anti-RBD and neutralizing antibodies in each subsequent dose, remaining at high titers until the end of follow-up. Group 1 had higher anti-RBD antibody titers than group 2 after beginning the primary regimen, with significant differences after the 2nd and 3rd doses. Group 2 showed a more expressive increase after the first booster with BNT162B2 (heterologous booster). Group 2 also presented high levels of neutralizing antibodies against the Gamma and Delta variants until five months after the second booster. In conclusion, the circulating levels of anti-RBD and neutralizing antibodies against the two variants of SARS-CoV-2 were durable even five months after the 4th dose, suggesting that periodic booster vaccinations (homologous or heterologous) induced long-lasting immunity.

The vine mealybug, Planococcus ficus, is a significant pest of vineyards in all major grape growing regions of the world. This pest causes significant aesthetic damage to berry clusters through its feeding behavior and secretion of ''honeydew'', which leads to significant decreases in crop marketability. More importantly, the vine mealybug is a vector of several grapevine viruses which are the causal agent of grapevine leafroll disease, one of the most destructive and economically devastating diseases of the grape industry worldwide. As there is no cure for grapevine leafroll disease, the only control measures available to reduce its spread are to remove infected vines whilst simultaneously controlling mealybug populations. Using transcriptomic libraries prepared from male and female mealybugs and a draft genome, we identified and evaluated expression levels of members of the odorant receptor gene family. Interestingly, of the 50 odorant receptors identified from these P. ficus genetic resources, only 23 were found to be expressed in females, suggesting this flightless life stage has a decreased reliance on the olfactory system. In contrast, 46 odorant receptors were found to be expressed in the alate male life stage. Heterologous expression of eight of these receptors, along with the obligate co-receptor, Orco, in HEK293 cells allowed for the identification of two receptors that respond to lavandulyl senecioate, the sole constituent of the sex pheromone used by this species. Interestingly, one of these receptors, PficOR8, also responded to the sex pheromone used by the Japanese mealybug, Planococcus kraunhiae. The data presented here represent the first report of odorant receptor gene family expression levels, as well as the identification of the first sex pheromone receptor, in soft-scale insects. The identification of a receptor for the vine mealybug sex pheromone will allow for the development of novel, species-specific pest control tools and monitoring devices.

In the development of new products by the industry, a rapid prototyping stage is recommended so that an initial version of the product can be evaluated. In this way, any necessary corrections can be applied while still in the prototyping stage, preventing design errors from reaching the final product. Augmented Reality (AR) and 3D Printing are techniques that have become ubiquitous in recent years due to the reduction of equipment costs. Several works in the area of rapid prototyping have been developed with one of these techniques in isolation; a few works have tried to unite these two tools. In this work, we propose a new functional rapid prototyping process, combining 3D Printing and AR to create functional interactive prototypes. This process is accomplished by projecting the AR onto the 3D-printed prototype. It interprets the user’s gestures on the physical prototype, converting clicks and touches into actions to be executed on the AR virtual prototype, making the prototype functional and interactive. The proposed system is evaluated by means of case studies and the application of the UEQ (User Experience Questionnaire) to users who have tested the system. This way, it is possible to evaluate the relevance of the proposed process.

The phyllosphere encompasses leaves and other aerial tissues of plants, which together provide diverse habitats for micro- and macro-organisms. In this editorial for the Phytobiomes Journal Focus Issue on the Phyllosphere, we celebrate the tremendous growth and impact of phyllosphere science as a discipline by introducing and providing context for 14 articles by nearly 100 authors from over 40 institutions. These articles collectively highlight the current status of the field and offer ideas for future directions. They explore topics related to phyllosphere biodiversity, community assembly and dynamics, and the adaptive capacity of species, populations, and communities on leaf surfaces and other phyllosphere compartments. The articles also delve into the multipartite relationships that phyllosphere colonizers have with each other and with their host, and issues of global concern such as food security, food safety, and climate change. This collection of work illustrates the international, transdisciplinary and collaborative nature of phyllosphere science, the challenges that the discipline faces, and the importance of recruiting and training the next generation of phyllosphere scientists.

Abstract Mesial temporal lobe epilepsy, one of the most common forms of epilepsy, is often linked with drug resistance. Surgical intervention is a reliable and safe treatment option, though research into postsurgical outcomes in our locality remains limited. We performed a retrospective observational study included 91 patients with mesial temporal lobe epilepsy and hippocampal sclerosis who had undergone anterior temporal lobectomy between 2012 and 2020 at a surgical epilepsy center located in Lima, Peru. Postoperative outcomes were analyzed using bivariate and multivariate analysis based on the Engel classification. We found that after 12 months of follow‐up, 78.65% of the 91 patients achieved an Engel IA classification, while 9.09% attained Engel IB classification and 11.24% were designated as Engel II, with only 1.12% classified as Engel IVA. The median QOLIE31 score was 84 (IQR: 75–90), with 74.16% of the participants successfully reintegrating into academic or employment activities. After 24 months, only 68 patients completed the follow‐up, with 69.12% achieving an Engel IA classification. Individuals with a secondary education or higher were more likely to achieve an Engel IA classification at 12 months (OR: 5.11; P = 0.005; CI: 1.63–16.01), after adjusting for sex and age. We concluded that most patients exhibited favorable outcomes after 1 year of follow‐up. However, lower educational attainment was linked to worse postsurgical outcomes.

Abstract Background Anemia is associated with impaired physical performance and adverse perioperative outcomes. Iron-deficiency anemia is increasingly treated with intravenous iron before elective surgery. We explored the relationship between exercise capacity, anemia, and total hemoglobin mass (tHb-mass) and the response to intravenous iron in anemic patients prior to surgery. Methods A prospective clinical study was undertaken in patients having routine cardiopulmonary exercise testing (CPET) with a hemoglobin concentration ([Hb])

A dual phase (DP500/800) steel sheet (1.6 mm thickness) was evaluated by means of low cycle fatigue (LCF). The fatigue properties of the material were assessed by means of the cyclic elastic modulus determination at half-life as well as by the plastic strain amplitude measurements. Both methods show a good correlation and high reliability, however, the plastic strain amplitude approach tends to fit better to the experimental results. From a parametric analysis performed, it was observed that the plastic strain amplitude approximation could be more suitable to assess the fatigue properties for LCF of the material due to an improved correlation of the computed cyclic elastic modulus in comparison to the cyclic elastic modulus measurements at half-life. Both methods showed that, for strain amplitudes higher than εa = 0.004, the cyclic elastic modulus tends to be lower than 210 GPa, meanwhile for lower strain amplitudes, the cyclic elastic modulus tends to increase. An evaluation by X-ray Diffraction technique allowed to determine that the increment of residual equivalent strain contributes to the cyclic elastic modulus diminution.

Abstract Non-contrast head CT (NCCT) is extremely insensitive for early ( 0.98). When this 150 CT test set was expanded to include a total of 364 CT scans with a more heterogeneous distribution of infarct locations (94 stroke-negative, 270 stroke-positive mixed territory infarcts), model sensitivity was 97%, specificity 99%, for detection of infarcts larger than the 70 mL volume threshold used for patient selection in several major randomized controlled trials of thrombectomy treatment.

The transfacet minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a novel approach available for the management of lumbar spondylolisthesis. It avoids the need to manipulate either of the exiting or traversing nerve roots, both protected by the bony boundaries of the approach. With the advancement in operative technologies such as navigation, mapping, segmentation, and augmented reality (AR), surgeons are prompted to utilize these technologies to enhance their surgical outcomes. A 36-year-old male patient was complaining of chronic progressive lower back pain. He was found to have grade 2 L4/5 spondylolisthesis. We studied the feasibility of a trans-Kambin or a transfacet MIS-TLIF, and decided to proceed with the latter given the wider corridor it provides. Preoperative trajectory planning and level segmentation in addition to intraoperative navigation and image merging were all utilized to provide an AR model to guide us through the surgery. The use of AR can build on the safety and learning of novel surgical approaches to spine pathologies. However, larger high-quality studies are needed to further objectively analyze its impact on surgical outcomes and to expand on its application.

ABSTRACT Erysiphe necator is an obligate fungal pathogen that causes grape powdery mildew, globally the most important disease on grapevines. Previous attempts to obtain a quality genome assembly for this pathogen were hindered by its high repetitive DNA content. Here, chromatin conformation capture (Hi-C) with long-read PacBio sequencing was combined to obtain a chromosome-scale assembly and a high-quality annotation for E. necator isolate EnFRAME01. The resulting 81.1 Mb genome assembly is 98% complete and consists of 34 scaffolds, 11 of which represent complete chromosomes. All chromosomes contain large centromeric-like regions and lack synteny to the 11 chromosomes of the cereal PM pathogen Blumeria graminis. Further analysis of their composition showed that repeats and transposable elements (TEs) occupy 62.7% of their content. TEs were almost evenly interspersed outside centromeric and telomeric regions and massively overlapped with regions of annotated genes, suggesting that they could have a significant functional impact. Abundant gene duplicates were observed as well, particularly in genes encoding candidate secreted effector proteins. Moreover, younger in age gene duplicates exhibited more relaxed selection pressure and were more likely to be located physically close in the genome than older duplicates. A total of 122 genes with copy number variations among six isolates of E. necator were also identified and were enriched in genes that were duplicated in EnFRAME01, indicating they may reflect an adaptive variation. Taken together, our study illuminates higher-order genomic architectural features of E. necator and provides a valuable resource for studying genomic structural variations in this pathogen. IMPORTANCE Grape powdery mildew caused by the ascomycete fungus Erysiphe necator is economically the most important and recurrent disease in vineyards across the world. The obligate biotrophic nature of E. necator hinders the use of typical genetic methods to elucidate its pathogenicity and adaptation to adverse conditions, and thus comparative genomics has been a major method to study its genome biology. However, the current reference genome of E. necator isolate C-strain is highly fragmented with many non-coding regions left unassembled. This incompleteness prohibits in-depth comparative genomic analyses and the study of genomic structural variations (SVs) that are known to affect several aspects of microbial life, including fitness, virulence, and host adaptation. By obtaining a chromosome-scale genome assembly and a high-quality gene annotation for E. necator, we reveal the organization of its chromosomal content, unearth previously unknown features of its biology, and provide a reference for studying genomic SVs in this pathogen.

Abstract Background Cancer evolution consists of a stepwise acquisition of genetic and epigenetic changes, which alter the gene expression profiles of cells in a particular tissue and result in phenotypic alterations acted upon by natural selection. The recurrent appearance of specific genetic lesions across individual cancers and cancer types suggests the existence of certain “driver mutations,” which likely make up the major contribution to tumors’ selective advantages over surrounding normal tissue and as such are responsible for the most consequential aspects of the cancer cells’ gene expression patterns and phenotypes. We hypothesize that such mutations are likely to cluster with specific dichotomous shifts in the expression of the genes they most closely control, and propose GMMchi, a Python package that leverages Gaussian Mixture Modeling to detect and characterize bimodal gene expression patterns across cancer samples, as a tool to analyze such correlations using 2 × 2 contingency table statistics. Results Using well-defined simulated data, we were able to confirm the robust performance of GMMchi, reaching 85% accuracy with a sample size of n = 90. We were also able to demonstrate a few examples of the application of GMMchi with respect to its capacity to characterize background florescent signals in microarray data, filter out uninformative background probe sets, as well as uncover novel genetic interrelationships and tumor characteristics. Our approach to analysing gene expression analysis in cancers provides an additional lens to supplement traditional continuous-valued statistical analysis by maximizing the information that can be gathered from bulk gene expression data. Conclusions We confirm that GMMchi robustly and reliably extracts bimodal patterns from both colorectal cancer (CRC) cell line-derived microarray and tumor-derived RNA-Seq data and verify previously reported gene expression correlates of some well-characterized CRC phenotypes. Availability The Python package GMMchi and our cell line microarray data used in this paper is available for downloading on GitHub at https://github.com/jeffliu6068/GMMchi .

Summary: Acidic environments reduce the intracellular pH (pHi) of most cells to levels that are sub-optimal for growth and cellular functions. Yet, cancers maintain an alkaline cytoplasm despite low extracellular pH (pHe). Raised pHi is thought to be beneficial for tumor progression and invasiveness. However, the transport mechanisms underpinning this adaptation have not been studied systematically. Here, we characterize the pHe-pHi relationship in 66 colorectal cancer cell lines and identify the acid-loading anion exchanger 2 (AE2, SLC4A2) as a regulator of resting pHi. Cells adapt to chronic extracellular acidosis by degrading AE2 protein, which raises pHi and reduces acid sensitivity of growth. Acidity inhibits mTOR signaling, which stimulates lysosomal function and AE2 degradation, a process reversed by bafilomycin A1. We identify AE2 degradation as a mechanism for maintaining a conducive pHi in tumors. As an adaptive mechanism, inhibiting lysosomal degradation of AE2 is a potential therapeutic target.

The kidney plays a central role in maintaining the fluid and electrolyte homeostasis in the body. Bicarbonate transporters NBCn1, NBCn2, and AE2 are expressed at the basolateral membrane of the medullary thick ascending limb (mTAL). In a previous study, NBCn1, NBCn2, and AE2 are proposed to play as a regulatory pathway to decrease NaCl reabsorption in the mTAL under high salt condition. When heterologously expressed, the activity of these transporters could be stimulated by the InsP3R binding protein released with inositol 1,4,5-trisphosphate (IRBIT), L-IRBIT (collectively the IRBITs), or protein phosphatase PP1. In the present study, we characterized by immunofluorescence the expression and localization of the IRBITs, and PP1 in rat kidney. Our data showed that the IRBITs were predominantly expressed from the mTAL through the distal renal tubules. PP1 was predominantly expressed in the TAL, but is also present in high abundance from the distal convoluted tubule through the medullary collecting duct. Western blotting analyses showed that the abundances of NBCn1, NBCn2, and AE2 as well as the IRBITs and PP1 were greatly upregulated in rat kidney by dietary sodium. Co-immunoprecipitation study provided the evidence for protein interaction between NBCn1 and L-IRBIT in rat kidney. Taken together, our data suggest that the IRBITs and PP1 play an important role in sodium handling in the kidney. We propose that the IRBITs and PP1 stimulates NBCn1, NBCn2, and AE2 in the basolateral mTAL to inhibit sodium reabsorption under high sodium condition. Our study provides important insights into understanding the molecular mechanism for the regulation of sodium homeostasis in the body.

In George Wald’s Nobel Prize acceptance speech for “discoveries concerning the primary physiological and chemical visual processes in the eye”, he noted that events after the activation of rhodopsin are too slow to explain visual reception. Photoreceptor membrane phosphoglycerides contain near-saturation amounts of the omega-3 fatty acid docosahexaenoic acid (DHA). The visual response to a photon is a retinal cis–trans isomerization. The trans-state is lower in energy; hence, a quantum of energy is released equivalent to the sum of the photon and cis–trans difference. We hypothesize that DHA traps this energy, and the resulting hyperpolarization extracts the energized electron, which depolarizes the membrane and carries a function of the photon’s energy (wavelength) to the brain. There, it contributes to the creation of the vivid images of our world that we see in our consciousness. This proposed revision to the visual process provides an explanation for these previously unresolved issues around the speed of information transfer and the purity of conservation of a photon’s wavelength and supports observations of the unique and indispensable role of DHA in the visual process.

Coronavirus has a lipid membrane. Whist replication requires hijacking the RNA tools of the host to synthesize virion protein, that then has to be wrapped in a lipid membrane to enable the budding off which extends the infection. Recent studies implicate certain essential fatty acids with replication suppression properties. The lipid membrane is commonly thought of as a fatty barrier to water solubles. It is however highly ordered and compositionally specific to cellular and sub cellular functions. There will likely also be an optimum specificity for the viral coat. Whist DNA, RNA and protein compositions are not affected by diet, the lipid membrane is. Moreover, the greater sensitivity of males over females to inadequacy of these essential fatty acids and membrane integrity has been known since the 1960s. With evidence that arachidonic and docosahexaenoic acids exhibiting anti-viral, immune, anti-inflammatory, blood pressure control and resolvin activity, their status needs to be urgently examined in relation to the prevention and therapy for Covid-19. It would also be advisable to re-assess food policy. The lipid requirements for the membrane rich systems as in the brain, nervous, vascular and immune systems have not been considered. There is little doubt these were significant in shaping the human genome over several million years. Departure from such conditions would be predicted to put populations at risk to disorder and infection, with males being more at risk than females.

(1º parágrafo do artigo) O que se vai ler é uma tentativa de colocar os dados disponíveis dentro de um “modelo” de “modernização”. As colocações dos vários dados não completam, sistematicamente, o quadro que se pretendia preenchido. Tal fato é devido à falta de novas e importantes pesquisas. Infelizmente não se pode equacionar, convenientemente, o tema, dada a precariedade das informações obtidas e, aqui, compendiadas. Caracteriza-se, pois, com este estudo preliminar, a necessidade de um planejamento conveniente de pesquisa, a ser efetuada, para a verificação dos fatores positivos e negativos da “modernização” face à imigração para o Estado de Santa Catarina.

IntroductionThe objective of this study is to assess the role of age at first exposure (AFE) to soccer heading as a predictor of known adverse associations of recent and longer-term heading with brain microstructure, cognitive, and behavioral features among adult amateur soccer players.MethodsThe sample included 276 active amateur soccer players (196 male and 81 female) aged 18–53 years old. AFE to soccer heading was treated as a binary variable, dichotomized at ≤ 10 years vs. >10 years old, based on a recently promulgated US Soccer policy, which bans heading for athletes ages 10 and under.ResultsWe found that soccer players who began heading at age 10 or younger performed better on tests of working memory (p = 0.03) and verbal learning (p = 0.02), while accounting for duration of heading exposure, education, sex, and verbal intelligence. No difference in brain microstructure or behavioral measures was observed between the two exposure groups.DiscussionThe findings indicate that, among adult amateur soccer players, AFE to heading before age 10 compared to later start of heading, is not associated with adverse outcomes, and may be associated with better cognitive performance in young adulthood. Cumulative heading exposure across the lifespan, rather than early life exposure, may drive risk for adverse effects and should be the focus of future longitudinal studies to inform approaches to enhance player safety.

One approach to studying the recognition of scenes and objects relies on the comparison of eye movement patterns during encoding and recognition. Past studies typically analyzed the perception of flat stimuli of limited extent presented on a computer monitor that did not require head movements. In contrast, participants in the present study saw omnidirectional panoramic scenes through an immersive 3D virtual reality viewer, and they could move their head freely to inspect different parts of the visual scenes. This allowed us to examine how unconstrained observers use their head and eyes to encode and recognize visual scenes. By studying head and eye movement within a fully immersive environment, and applying cross-recurrence analysis, we found that eye movements are strongly influenced by the content of the visual environment, as are head movements-though to a much lesser degree. Moreover, we found that the head and eyes are linked, with the head supporting, and by and large mirroring the movements of the eyes, consistent with the notion that the head operates to support the acquisition of visual information by the eyes.

When we imagine a picture, we move our eyes even though the picture is physically not present. These eye movements provide information about the ongoing process of mental imagery. Eye movements unfold over time, and previous research has shown that the temporal gaze dynamics of eye movements in mental imagery have unique properties, which are unrelated to those in perception. In mental imagery, refixations of previously fixated locations happen more often and in a more systematic manner than in perception. The origin of these unique properties remains unclear. We tested how the temporal structure of eye movements is influenced by the complexity of the mental image. Participants briefly saw and then maintained a pattern stimulus, consisting of one (easy condition) to four black segments (most difficult condition). When maintaining a simple pattern in imagery, participants restricted their gaze to a narrow area, and for more complex stimuli, eye movements were more spread out to distant areas. At the same time, fewer refixations were made in imagery when the stimuli were complex. The results show that refixations depend on the imagined content. While fixations of stimulus-related areas reflect the so-called ‘looking at nothing’ effect, gaze restriction emphasizes differences between mental imagery and perception.

Abstract Background Electronic health records (EHR) data can be used to understand population level quality of care especially when supplemented with patient reported data. However, survey non-response can result in biased population estimates. As a case study, we demonstrate that EHR and survey data can be combined to estimate primary care population prescription treatment status for migraine stratified by migraine disability, without and with adjustment for survey non-response bias. We selected disability as it is associated with survey participation and patterns of prescribing for migraine. Methods A stratified random sample of Sutter Health adult primary care (PC) patients completed a digital survey about headache, migraine, and migraine related disability. The survey data from respondents with migraine were combined with their EHR data to estimate the proportion who had prescription orders for acute or preventive migraine treatments. Separate proportions were also estimated for those with mild disability (denoted “mild migraine”) versus moderate to severe disability (denoted mod-severe migraine) without and with correction, using the inverse propensity weighting method, for non-response bias. We hypothesized that correction for non-response bias would result in smaller differences in proportions who had a treatment order by migraine disability status. Results The response rate among 28,268 patients was 8.2%. Among survey respondents, 37.2% had an acute treatment order and 16.8% had a preventive treatment order. The response bias corrected proportions were 26.2% and 11.6%, respectively, and these estimates did not differ from the total source population estimates (i.e., 26.4% for acute treatments, 12.0% for preventive treatments), validating the correction method. Acute treatment orders proportions were 32.3% for mild migraine versus 37.3% for mod-severe migraine and preventive treatment order proportions were 12.0% for mild migraine and 17.7% for mod-severe migraine. The response bias corrected proportions for acute treatments were 24.8% for mild migraine and 26.6% for mod-severe migraine and the proportions for preventive treatment were 8.1% for mild migraine and 12.0% for mod-severe migraine. Conclusions In this study, we combined survey data with EHR data to better understand treatment needs among patients diagnosed with migraine. Migraine-related disability is directly related to preventive treatment orders but less so for acute treatments. Estimates of treatment status by self-reported disability status were substantially over-estimated among those with moderate to severe migraine-related disability without correction for non-response bias.

The genomic causes and clinical manifestations of hereditary colorectal cancer (HCRC) might be stratified into 2 groups, namely, familial (FCRC) and a limited sense of HCRC, respectively. Otherwise, FCRC is canonically classified into 2 major categories; Lynch syndrome (LS) or associated spectra and inherited polyposis syndrome. By contrast, despite an increasing body of genotypic and phenotypic traits, some FCRC cannot be clearly differentiated as definitively single type, and the situation has become more complex as additional causative genes have been discovered. This review provides an overview of HCRC, including 6 LS or associated spectra and 8 inherited polyposis syndromes, according to molecular pathogenesis. Variants and newly-identified FCRC are particularly emphasized, including MUTYH (or MYH)-associated polyposis, Muir-Torre syndrome, constitutional mismatch repair deficiency, EPCAM-associated LS, polymerase proofreading-associated polyposis, RNF43- or NTHL1-associated serrated polyposis syndrome, PTEN hamartoma tumor syndrome, and hereditary mixed polyposis syndrome. We also comment on the clinical utility of multigene panel tests, focusing on comprehensive cancer panels that include HCRC. Finally, HCRC surveillance strategies are recommended, based on revised or notable concepts underpinned by competent validation and clinical implications, and favoring major guidelines. As hereditary syndromes are mainly attributable to genomic constitutions of distinctive ancestral groups, an integrative national HCRC registry and guideline is an urgent priority.

Abstract Laboratory data from Electronic Health Records (EHR) are often used in prediction models where estimation bias and model performance from missingness can be mitigated using imputation methods. We demonstrate the utility of imputation in two real-world EHR-derived cohorts of ischemic stroke from Geisinger and of heart failure from Sutter Health to: (1) characterize the patterns of missingness in laboratory variables; (2) simulate two missing mechanisms, arbitrary and monotone; (3) compare cross-sectional and multi-level multivariate missing imputation algorithms applied to laboratory data; (4) assess whether incorporation of latent information, derived from comorbidity data, can improve the performance of the algorithms. The latter was based on a case study of hemoglobin A1c under a univariate missing imputation framework. Overall, the pattern of missingness in EHR laboratory variables was not at random and was highly associated with patients’ comorbidity data; and the multi-level imputation algorithm showed smaller imputation error than the cross-sectional method.

El objetivo de la investigación es analizar las competencias de emprendimiento en estudiantes universitarios peruanos, específicamente de una universidad privada del Perú. La investigación fue de tipo aplicada, de diseño cuasi experimental se utilizó el enfoque cuantitativo, de alcance descriptivo y con corte longitudinal. Se aplicó la metodología “Conozca de empresa” de la Organización Internacional del Trabajo para desarrollar competencias en emprendimiento. Con el apoyo del cuestionario se midieron variables en dos ocasiones: la primera en el pretest, cuyos resultados más relevantes indicaron en el 79% de los casos, los estudiantes son persistentes, en el 71% ingeniosos, y el 75% tienen aversión al riesgo. En la segunda en el post test, los resultados más resaltantes indican, que el 98% logró desarrollar el programa a una situación real, el 97% se consideran con talento para diseñar planes, y el 98% se consideran futuros empresarios. Concluyéndose que el 68% de los estudiantes universitarios evaluados (42) desarrollaron competencias de emprendimiento de nivel alto, y, de estos, el 98% (41) llevó el programa a una situación real de mercado con la aplicación de la metodología “Conozca de empresa” de la Organización Internacional del Trabajo.

We aimed to continuously determine the stroke volume (SV) and blood volume (BV) during incremental exercise to evaluate the individual SV course and to correlate both variables across different exercise intensities. Twenty-six females with heterogeneous endurance capacities performed an incremental cycle ergometer test to continuously determine the oxygen uptake (V̇O2), cardiac output (Q̇) and changes in BV. Q̇ was determined by impedance cardiography and resting cardiac dimensions by 2D echocardiography. Hemoglobin mass and BV were determined using a carbon monoxide-rebreathing method. V̇O2max ranged from 32 to 62 mL·kg−1·min−1. Q̇max and SVmax ranged from 16.4 to 31.6 L·min−1 and 90–170 mL, respectively. The SV significantly increased from rest to 40% and from 40% to 80% V̇O2max. Changes in SV from rest to 40% V̇O2max were negatively (r = −0.40, p = 0.05), between 40% and 80% positively correlated with BV (r = 0.45, p < 0.05). At each exercise intensity, the SV was significantly correlated with the BV and the cardiac dimensions, i.e., left ventricular muscle mass (LVMM) and end-diastolic diameter (LVEDD). The BV decreased by 280 ± 115 mL (5.7%, p = 0.001) until maximum exercise. We found no correlation between the changes in BV and the changes in SV between each exercise intensity. The hemoglobin concentration [Hb] increased by 0.8 ± 0.3 g·dL−1, the capillary oxygen saturation (ScO2) decreased by 4.0% (p < 0.001). As a result, the calculated arterial oxygen content significantly increased (18.5 ± 1.0 vs. 18.9 ± 1.0 mL·dL−1, p = 0.001). A 1 L higher BV at V̇O2max was associated with a higher SVmax of 16.2 mL (r = 0.63, p < 0.001) and Q̇max of 2.5 L·min−1 (r = 0.56, p < 0.01). In conclusion, the SV strongly correlates with the cardiac dimensions, which might be the result of adaptations to an increased volume load. The positive effect of a high BV on SV is particularly noticeable at high and severe intensity exercise. The theoretically expected reduction in V̇O2max due to lower SV as a consequence of reduced BV is apparently compensated by the increased arterial oxygen content due to a higher [Hb].

Growth of cancer cells in vitro can be attenuated by genetically inactivating selected metabolic pathways. However, loss-of-function mutations in metabolic pathways are not negatively selected in human cancers, indicating that these genes are not essential in vivo. We hypothesize that spontaneous mutations in ‘metabolic genes’ will not necessarily produce functional defects because mutation-bearing cells may be rescued by metabolite exchange with neighboring wild-type cells via gap junctions. Using fluorescent substances to probe intercellular diffusion, we show that colorectal cancer (CRC) cells are coupled by gap junctions assembled from connexins, particularly Cx26. Cells with genetically inactivated components of pH regulation (SLC9A1), glycolysis (ALDOA), or mitochondrial respiration (NDUFS1) could be rescued through access to functional proteins in co-cultured wild-type cells. The effect of diffusive coupling was also observed in co-culture xenografts. Rescue was largely dependent on solute exchange via Cx26 channels, a uniformly and constitutively expressed isoform in CRCs. Due to diffusive coupling, the emergent phenotype is less heterogenous than its genotype, and thus an individual cell should not be considered as the unit under selection, at least for metabolite-handling processes. Our findings can explain why certain loss-of-function mutations in genes ascribed as ‘essential’ do not influence the growth of human cancers.

We wanted to determine the influence of total blood volume (BV) and blood lactate quantity on lactate concentrations during incremental exercise. Twenty-six healthy, nonsmoking, heterogeneously trained females (27.5 ± 5.9 ys) performed an incremental cardiopulmonary exercise test on a cycle ergometer during which maximum oxygen uptake (V·O2max), lactate concentrations ([La−]) and hemoglobin concentrations ([Hb]) were determined. Hemoglobin mass and blood volume (BV) were determined using an optimised carbon monoxide-rebreathing method. V·O2max and maximum power (Pmax) ranged between 32 and 62 mL·min−1·kg−1 and 2.3 and 5.5 W·kg−1, respectively. BV ranged between 81 and 121 mL·kg−1 of lean body mass and decreased by 280 ± 115 mL (5.7%, p = 0.001) until Pmax. At Pmax, the [La−] was significantly correlated to the systemic lactate quantity (La−, r = 0.84, p < 0.0001) but also significantly negatively correlated to the BV (r = −0.44, p < 0.05). We calculated that the exercise-induced BV shifts significantly reduced the lactate transport capacity by 10.8% (p < 0.0001). Our results demonstrate that both the total BV and La− have a major influence on the resulting [La−] during dynamic exercise. Moreover, the blood La− transport capacity might be significantly reduced by the shift in plasma volume. We conclude, that the total BV might be another relevant factor in the interpretation of [La−] during a cardio-pulmonary exercise test.

Patients with chronic mountain sickness (CMS) have a high hemoglobin concentration [Hb] due to increased hemoglobin mass (Hbmass) and possibly reduced plasma volume (PV). The values of Hbmass, PV and blood volume (BV) have been described differently, and the relationships between [Hb] and Hbmass or PV are poorly understood. This study obtained representative Hbmass, PV and BV data from healthy, high-altitude residents and CMS patients and quantified the dependency of [Hb] on Hbmass and PV. Methods: Eighty-seven subjects born at high altitude (∼3,900 m) were enrolled. Thirty-four had CMS (CMS), 11 had polycythemia without CMS (intermediate, IM), 20 were healthy highlanders (HH), and 22 living near sea level (SL, 420 m) served as the sea level (SL) control group. Hbmass, PV and BV were determined using a CO-rebreathing method modified for assessing polycythemia patients. Furthermore, [Hb], hematocrit (Hct), plasma erythropoietin concentration [EPO] and blood gas and acid–base status were determined. Results: In the HH group, Hbmass was 27% higher (940 ± 105 g) than in the SL group (740 ± 112 g) and 72% (1,617 ± 265 g) lower than in the CMS group. The PV in the HH group was similar to that in the SL group (−6%) and 15% higher than that in the CMS group (p < 0.001). In the HH group, the BV (5,936 ± 673 ml) did not differ from that in the SL group and was 28% lower than in the CMS group (7,606 ± 1075 ml, p < 0.001). Log [EPO] was slightly increased in the CMS group relative to the HH group (p < 0.01). All values in the IM group were between those in the HH and CMS groups. Hbmass and BV were positively correlated, and PV was negatively correlated with peripheral O2 saturation. Increased Hbmass and decreased PV contributed approximately 65 and 35%, respectively, to the difference in [Hb] between the HH (17.1 ± 0.8 g/dl) and CMS (22.1 ± 1.0 g/dl) groups. Conclusions: In CMS patients, the decrease in PV only partially compensated for the substantial increase in Hbmass, but it did not prevent an increase in BV; the decrease in PV contributed to an excessively high [Hb].

Carbonic anhydrases (CAs), because they catalyze the interconversion of carbon dioxide (CO2) and water into bicarbonate (HCO3−) and protons (H+), thereby influencing pH, are near the core of virtually all physiological processes in the body. In the kidneys, soluble and membrane-associated CAs and their synergy with acid–base transporters play important roles in urinary acid secretion, the largest component of which is the reabsorption of HCO3− in specific nephron segments. Among these transporters are the Na+-coupled HCO3− transporters (NCBTs) and the Cl−-HCO3− exchangers (AEs)—members of the “solute-linked carrier” 4 (SLC4) family. All of these transporters have traditionally been regarded as “HCO3−“ transporters. However, recently our group has demonstrated that two of the NCBTs carry CO32− rather than HCO3− and has hypothesized that all NCBTs follow suit. In this review, we examine current knowledge on the role of CAs and “HCO3−” transporters of the SLC4 family in renal acid–base physiology and discuss how our recent findings impact renal acid secretion, including HCO3− reabsorption. Traditionally, investigators have associated CAs with producing or consuming solutes (CO2, HCO3−, and H+) and thus ensuring their efficient transport across cell membranes. In the case of CO32− transport by NCBTs, however, we hypothesize that the role of membrane-associated CAs is not the appreciable production or consumption of substrates but the minimization of pH changes in nanodomains near the membrane.

Summary: Unlike most cell types, many cancer cells survive at low extracellular pH (pHe), a chemical signature of tumors. Genes that facilitate survival under acid stress are therefore potential targets for cancer therapies. We performed a genome-wide CRISPR-Cas9 cell viability screen at physiological and acidic conditions to systematically identify gene knockouts associated with pH-related fitness defects in colorectal cancer cells. Knockouts of genes involved in oxidative phosphorylation (NDUFS1) and iron-sulfur cluster biogenesis (IBA57, NFU1) grew well at physiological pHe, but underwent profound cell death under acidic conditions. We identified several small-molecule inhibitors of mitochondrial metabolism that can kill cancer cells at low pHe only. Xenografts established from NDUFS1−/− cells grew considerably slower than their wild-type controls, but growth could be stimulated with systemic bicarbonate therapy that lessens the tumoral acid stress. These findings raise the possibility of therapeutically targeting mitochondrial metabolism in combination with acid stress as a cancer treatment option.

IntroductionEsports is practiced by millions of people worldwide every day. On a professional level, esports has been proven to have a high stress potential and is sometimes considered equivalent to traditional sporting activities. While traditional sports have health-promoting effects through muscle activity and increased energy expenditure, amateur esports could represent a purely sedentary activity, which would carry potentially harmful effects when practiced regularly. Therefore, this study aims to investigate the acute effects of esports on the cardiovascular system and energy expenditure in amateur esports players to show whether esports can be considered as physical strain or mental stress or whether amateur esports has to be seen as purely sedentary behavior.MethodsThirty male subjects participated in a 30-min gaming session, playing the soccer simulation game FIFA 20 or the tactical, first-person multiplayer shooter Counter-Strike: Global Offensive. Respiratory and cardiovascular parameters, as well as energy expenditure, blood glucose, lactate, and cortisol, were determined pre-, during, and post-gaming.ResultsThere were no significant changes in oxygen uptake, carbon dioxide output, energy expenditure, stroke volume, or lactate levels. Heart rate, blood glucose and cortisol decreased through the intervention until reaching their minimum levels 10 min post-gaming (Cortisolpre: 3.1 ± 2.9 ng/ml, Cortisolpost: 2.2 ± 2.3 ng/ml, p < 0.01; HRmin0.5: 82 ± 11 bpm, HRpost: 74 ± 13 bpm, p < 0.01).ConclusionA 30-min esports intervention does not positively affect energy expenditure or metabolism in amateur esports players. Therefore, it cannot provide the same health-promoting effects as traditional sports participation, but could in the long-term rather cause the same potentially health-damaging effects as purely sedentary behavior. However, it does not trigger a negative stress response in the players. Deliberate physical activity and exercise routines adapted to these demands should therefore be part of the daily life of amateur esports players.

Cadmium (Cd) is a highly toxic heavy metal considered carcinogenic to humans. The adsorption behavior of cadmium adsorption using untreated and chemically modified rice husk was investigated. Experimental tests were carried out to evaluate the influence of the variables pH, initial concentration of cadmium, and dosage of adsorbent in the adsorption process. In optimal experimental conditions, the maximum adsorption efficiency was 92.65%. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) were used allowing the identification of the main functional groups and morphology of rice husk and treated rice husk, and the results showed an improvement of adsorption characteristics after rice husk treatment with NaOH. The optimum adsorption pH for both types of rice husk was 7. The maximum adsorption capacities of RH and treated RH fitted by the Langmuir model were 5.13 mg/g and 11.06 mg/g, respectively. The pseudosecond order kinetics has the best coefficients of determination for untreated (R2=0.992) and treated (R2=0.999) rice husk. The adsorption process was found to be endothermic in nature with enthalpy of 14.08 kJ/mol and entropy of 170.98 J/mol.K. The calculated activation energy was 24 kJ/mol. The results showed the potential of rice husk as a low-cost, easily managed, and efficient biosorbent for Cd removal from waters.

Communications between clinicians and patients with idiopathic pulmonary fibrosis (IPF) have the potential to be challenging. The variable course and poor prognosis of IPF complicate discussions around life expectancy but should not prevent clinicians from having meaningful conversations about patients’ fears and needs, while acknowledging uncertainties. Patients want information about the course of their disease and management options, but the provision of information needs to be individualised to the needs and preferences of the patient. Communication from clinicians should be empathetic and take account of the patient's perceptions and concerns. Models, tools and protocols are available that can help clinicians to improve their interactions with patients. In this article, we consider the difficulties inherent in discussions with patients with IPF and their loved ones, and how clinicians might communicate with patients more effectively, from breaking the news about the diagnosis to providing support throughout the course of the disease.

Abstract Purpose The aim of this study was to examine whether the translocator protein 18-kDa (TSPO) PET ligand [18F]FEPPA has the sensitivity for detecting changes in CD68-positive microglial/macrophage activation in hemiparkinsonian rhesus macaques treated with allogeneic grafts of induced pluripotent stem cell-derived midbrain dopaminergic neurons (iPSC-mDA). Methods In vivo positron emission tomography (PET) imaging with [18F]FEPPA was used in conjunction with postmortem CD68 immunostaining to evaluate neuroinflammation in the brains of hemiparkinsonian rhesus macaques (n = 6) that received allogeneic iPSC-mDA grafts in the putamen ipsilateral to MPTP administration. Results Based on assessment of radiotracer uptake and confirmed by visual inspection of the imaging data, nonhuman primates with allogeneic grafts showed increased [18F]FEPPA binding at the graft sites relative to the contralateral putamen. From PET asymmetry analysis of the images, the mean asymmetry index of the monkeys was AI = − 0.085 ± 0.018. Evaluation and scoring of CD68 immunoreactivity by an investigator blind to the treatment identified significantly more neuroinflammation in the grafted areas of the putamen compared to the contralateral putamen (p = 0.0004). [18F]FEPPA PET AI showed a positive correlation with CD68 immunoreactivity AI ratings in the monkeys (Spearman’s ρ = 0.94; p = 0.005). Conclusion These findings reveal that [18F]FEPPA PET is an effective marker for detecting increased CD68-positive microglial/macrophage activation and demonstrates sufficient sensitivity to detect changes in neuroinflammation in vivo following allogeneic cell engraftment.

The novel reactive methylmethacrylate (MMA) thermoplastic resin (commercially known as Elium® resin) is the first liquid thermoplastic resin which is curable at room temperature. This resin is a competitive solution against traditional epoxy-based composites. In this work, novel non-crimp (NC) glass fabric/MMA resin composites were manufactured using a vacuum infusion process. Cellulose microcrystals (CMCs) were dispersed in the resin to improve the fibre/matrix interface and the composite properties. CMCs were first dispersed in the resin using an ultrasonication process and then the CMC/MMA resin suspension, mixed with a peroxide initiator, was infused into the reinforcing fabric. The amounts of CMCs dispersed in the resin were 0.5%, 1% and 2% (of the weight of the resin). The influence of CMCs on the interlaminar shear strength (interface), flexural properties, abrasive wear and dynamic-mechanical behaviour was thoroughly investigated. From the mechanical characterisation, it was observed that the addition of 1% CMC to the NC glass/MMA resin composites improved the flexural strength, interlaminar shear strength and wear performance by 30.77%, 38.04% and 22.27%, respectively as compared to the neat glass/MMA resin composite. Above this amount of CMC (i.e., 1 wt%), the properties started to degrade as a result of CMC agglomeration.

We report the first case of Daratumumab interference of allogeneic crossmatch tests repeatedly causing aberrant false-positive results, which inadvertently delayed transplant for a waitlisted renal patient with multiple myeloma. Daratumumab is an IgG1κ human monoclonal antibody commonly used to treat multiple myeloma, characterized by cancerous plasma cells and often leads to renal failure requiring kidney transplant, by depleting CD38-expressing plasma cells. In this case study, the patient had end-stage renal disease secondary to multiple myeloma and was continuously receiving Daratumumab infusions. The patient did not have any detectable antibodies to human leukocyte antigens but repeatedly had unexpected positive crossmatch by the flow cytometry-based method with 26 of the 27 potential deceased organ donors, implying donor-recipient immunological incompatibility. However, further review and analysis suggested that the positive crossmatches were likely false-positive as a result of interference from Daratumumab binding to donor cell surface CD38 as opposed to the presence of donor-specific antibodies. The observed intensity of the false-positive crossmatches was also highly variable, potentially due to donor- and/or cell-dependent expression of CD38. The variability of CD38 expression was, therefore, for the first time, characterized on the T and B cells isolated from various tissues and peripheral blood of 78 individuals. Overall, T cells were found to have a lower CD38 expression profile than the B cells, and no significant difference was observed between deceased and living individuals. Finally, we show that a simple cell treatment by dithiothreitol can effectively mitigate Daratumumab interference thus preserving the utility of pre-transplant crossmatch in multiple myeloma patients awaiting kidney transplant.

En este artículo se analizan los métodos de investigación utilizados en las ponencias y comunicaciones presentadas en los simposios de la SEIEM, desde su constitución en 1997 hasta 2010. Se estudia la distribución temporal, método de investigación preferente, área problemática, nivel educativo y principales características metodológicas, comparando con otros informes en los que se analizan los métodos de investigación en educación matemática. Así mismo se describen las características de los trabajos que aplican métodos cuantitativos, cualitativos y mixtos, y se proporciona una guía de reflexión metodológica, junto con algunas recomendaciones para incrementar el rigor metodológico en la investigación en educación matemática.

We wanted to demonstrate the relationship between blood volume, cardiac size, cardiac output and maximum oxygen uptake (V.O2max) and to quantify blood volume shifts during exercise and their impact on oxygen transport. Twenty-four healthy, non-smoking, heterogeneously trained male participants (27 ± 4.6 years) performed incremental cycle ergometer tests to determine V.O2max and changes in blood volume and cardiac output. Cardiac output was determined by an inert gas rebreathing procedure. Heart dimensions were determined by 3D echocardiography. Blood volume and hemoglobin mass were determined by using the optimized CO-rebreathing method. The V.O2max ranged between 47.5 and 74.1 mL⋅kg–1⋅min–1. Heart volume ranged between 7.7 and 17.9 mL⋅kg–1 and maximum cardiac output ranged between 252 and 434 mL⋅kg–1⋅min–1. The mean blood volume decreased by 8% (567 ± 187 mL, p = 0.001) until maximum exercise, leading to an increase in [Hb] by 1.3 ± 0.4 g⋅dL–1 while peripheral oxygen saturation decreased by 6.1 ± 2.4%. There were close correlations between resting blood volume and heart volume (r = 0.73, p = 0.002), maximum blood volume and maximum cardiac output (r = 0.68, p = 0.001), and maximum cardiac output and V.O2max (r = 0.76, p < 0.001). An increase in maximum blood volume by 1,000 mL was associated with an increase in maximum stroke volume by 25 mL and in maximum cardiac output by 3.5 L⋅min–1. In conclusion, blood volume markedly decreased until maximal exhaustion, potentially affecting the stroke volume response during exercise. Simultaneously, hemoconcentrations maintained the arterial oxygen content and compensated for the potential loss in maximum cardiac output. Therefore, a large blood volume at rest is an important factor for achieving a high cardiac output during exercise and blood volume shifts compensate for the decrease in peripheral oxygen saturation, thereby maintaining a high arteriovenous oxygen difference.