Optimization of Exercise Countermeasures for Human Space Flight: Operational Considerations for Concurrent Strength and Aerobic Training

The physiological challenges presented by space flight and in microgravity (μG) environments are well documented. μG environments can result in declines muscle mass, contractile strength, and functional capabilities. Previous work has focused on exercise countermeasures designed to attenuate the negative effects of μG on skeletal muscle structure, function, and contractile strength and aerobic fitness parameters. Exposure to μG environments influences both strength and aerobic type physical qualities. As such, the current exercise recommendations for those experiencing μG involve a combination of strength and aerobic training or “concurrent training.” Concurrent training strategies can result in development and maintenance of both strength and aerobic capabilities. However, terrestrial research has indicated that if concurrent training strategies are implemented inappropriately, strength development can be inhibited. Previous work has also demonstrated that the aforementioned inhibition of strength development is dependent on the frequency of aerobic training, modality of aerobic training, the relief period between strength and aerobic training, and the intra-session sequencing of strength and aerobic training. While time constraints and feasibility are important considerations for exercise strategies in μG, certain considerations could be made when prescribing concurrent strength and aerobic training to those experiencing human space flight. If strength and aerobic exercise must be performed in close proximity, strength should precede aerobic stimulus. Eccentric strength training methods should be considered to increase mechanical load and reduce metabolic cost. For aerobic capacity, maintenance cycle and/or rowing-based high-intensity intermittent training (HIIT) should be considered and cycle ergometry and/or rowing may be preferable to treadmill running

The impact of overweight and obesity on health-related quality of life in childhood – results from an intervention study

<p>Abstract</p> <p>Background</p> <p>The negative impact of overweight (including obesity) and related treatment on children's and adolescents' health-related quality of life (HRQoL) has been shown in few specific samples thus far. We examined HRQoL and emotional well-being in overweight children from an outpatient treatment sample as well as changes of these parameters during treatment.</p> <p>Methods</p> <p>In a cross-sectional design, self-reported HRQoL of 125 overweight (including obese) children who contacted a treatment facility, but had not yet receive treatment, were compared to 172 children from randomly selected schools using independent two-sample t-tests. Additionally, in a longitudinal design, the overweight children were retested by administering the same questionnaire at the end of the intervention (after one year). It included measures such as the body mass index (BMI), the general health item (GHI), the KINDL^R, and the Child Dynamic Health Assessment Scale (ChildDynHA). Comparisons were based on dependent t-tests and the Wilcoxon signed-rank test.</p> <p>Results</p> <p>Overweight children showed statistically significant impairment in the GHI (Cohen's d = 0.59) and emotional well-being (ChildDynha) (d = 0.33) compared to the school children. With respect to HRQoL, the friends dimension of the KINDL^Rwas significantly impaired in the overweight group (d = 0.33). However, no impairment was found for the total HRQoL score or other KINDL^Rsubdimensions. Regarding the longitudinal part of our study, most of the children improved their BMI, but the majority (87.5%) remained overweight. Nevertheless, the participants' perceived health, emotional well-being, and generic as well as disease-specific HRQoL improved during intervention.</p> <p>Conclusion</p> <p>The findings emphasize the importance of patient-reported outcomes such as HRQoL. Even though overweight and obesity might accompany most of the children throughout their lifetime, the impairment associated with this chronic condition can be considerably reduced. Opportunities of health promotion in overweight/obese children and adolescents are discussed.</p

Metabolism of remimazolam in primary human hepatocytes during continuous long-term infusion in a 3-D bioreactor system

Background: Remimazolam is an ultra-short acting benzodiazepine under development for procedural sedation and general anesthesia. It is hydrolyzed by CES1 to an inactive metabolite (CNS7054). Purpose: In this study, the effect of continuous remimazolam exposure on its metabolism and on CES1 expression was investigated in a dynamic 3-D bioreactor culture model inoculated with primary human hepatocytes. Methods: Remimazolam was continuously infused into bioreactors for 5 days at a final concentration of 3,000 ng/ml (6.8 μM). In parallel, 2-D cultures were run with cells from the same donors, but with discontinuous exposure to remimazolam. Results: Daily measurement of clinical chemistry parameters (glucose, lactate, urea, ammonia, and liver enzymes) in culture supernatants indicated no noxious effect of remimazolam on hepatocyte integrity as compared to untreated controls. Concentrations of remimazolam reached steady-state values of around 250 ng/ml within 8 hours in 3-D bioreactors whereas in 2-D cultures remimazolam concentrations declined to almost zero within the same time frame. Levels of CNS7054 showed an inverse time-course reaching average values of 1,350 ng/ml in perfused 3-D bioreactors resp. 2,800 ng/ml in static 2-D cultures. Analysis of mRNA expression levels of CES1 indicated no changes in gene expression over the culture period. Conclusion: The results indicated a stable metabolism of remimazolam during 5 days of continuous exposure to clinically relevant concentrations of the drug. Moreover, there was no evidence for a harmful effect of remimazolam exposure on the integrity and metabolic activity of in vitro cultivated primary human hepatocytes

Reflexiones de la práctica profesional desde un área de museos municipal

En este trabajo relatamos una experiencia profesional de trabajo en el contexto de un espacio público municipal. La misma ocurre en un equipo de trabajo integrado tanto por arqueólogas que se desempeñan en investigación como por arqueólogas y antropólogos dedicados a la gestión, administración e investigación-acción en un área de museos. Ésta área incluye un Museo y Archivo Histórico y un Museo de Ciencias Naturales, ambos dependientes de la dirección General de Educación del estado municipal de la ciudad de Necochea. Específicamente nos interesa detallar las diversas dificultades presentes en nuestra labor diaria, a fines de reflexionar sobre las falencias en nuestra formación profesional, para desarrollarnos en tareas no estrictamente ligadas a las de investigación científica. En este sentido, explicitaremos algunos de los puntos de divergencia observados entre los espacios municipales y los ámbitos académicos, que plantean dinámicas y lógicas de trabajo profesional diferentes.An experience of professional practice in a public community context is described. The team involved includes archaeologists dedicated to research as well as an archaeologist and an anthropologist dedicated to management, administration and research -action activities in a museum area. This area has both a Historical Museum and a Natural Science Museum that belong to the General Education Department of the city council of Necochea. The difficulties encountered in everyday work lead us to consider the lack of training, in our academic system, in areas not strictly related to scientific research. We here assess some aspects where we have observed different professional work dynamics and logics between the public state and the academic environments.Fil: Caro Petersen, Agueda Aleli. Provincia de Buenos Aires. Municipalidad de Necochea. Museo de Ciencias Naturales de Necochea. Area de Arqueología y Antropología; ArgentinaFil: Colombo, Mariano Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Provincia de Buenos Aires. Municipalidad de Necochea. Museo de Ciencias Naturales de Necochea. Area de Arqueología y Antropología; ArgentinaFil: Flegenheimer, Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Provincia de Buenos Aires. Municipalidad de Necochea. Museo de Ciencias Naturales de Necochea. Area de Arqueología y Antropología; Argentin

RootPainter3D: Interactive-machine-learning enables rapid and accurate contouring for radiotherapy

Organ-at-risk contouring is still a bottleneck in radiotherapy, with many deep learning methods falling short of promised results when evaluated on clinical data. We investigate the accuracy and time-savings resulting from the use of an interactive-machine-learning method for an organ-at-risk contouring task. We compare the method to the Eclipse contouring software and find strong agreement with manual delineations, with a dice score of 0.95. The annotations created using corrective-annotation also take less time to create as more images are annotated, resulting in substantial time savings compared to manual methods, with hearts that take 2 minutes and 2 seconds to delineate on average, after 923 images have been delineated, compared to 7 minutes and 1 seconds when delineating manually. Our experiment demonstrates that interactive-machine-learning with corrective-annotation provides a fast and accessible way for non computer-scientists to train deep-learning models to segment their own structures of interest as part of routine clinical workflows. Source code is available at \href{https://github.com/Abe404/RootPainter3D}{this HTTPS URL}

Sodium channel endocytosis drives axon initial segment plasticity

Activity-dependent plasticity of the axon initial segment (AIS) endows neurons with the ability to adapt action potential output to changes in network activity. Action potential initiation at the AIS highly depends on the clustering of voltage-gated sodium channels, but the molecular mechanisms regulating their plasticity remain largely unknown. Here, we developed genetic tools to label endogenous sodium channels and their scaffolding protein, to reveal their nanoscale organization and longitudinally image AIS plasticity in hippocampal neurons in slices and primary cultures. We find that N-methyl-d-aspartate receptor activation causes both long-term synaptic depression and rapid internalization of AIS sodium channels within minutes. The clathrin-mediated endocytosis of sodium channels at the distal AIS increases the threshold for action potential generation. These data reveal a fundamental mechanism for rapid activity-dependent AIS reorganization and suggests that plasticity of intrinsic excitability shares conserved features with synaptic plasticity

Bioarchaeological evidence of one of the earliest Islamic burials in the Levant

Abstract: The Middle East plays a central role in human history harbouring a vast diversity of ethnic, cultural and religious groups. However, much remains to be understood about past and present genomic diversity in this region. Here we present a multidisciplinary bioarchaeological analysis of two individuals dated to the late 7th and early 8th centuries, the Umayyad Era, from Tell Qarassa, an open-air site in modern-day Syria. Radiocarbon dates and burial type are consistent with one of the earliest Islamic Arab burials in the Levant. Interestingly, we found genomic similarity to a genotyped group of modern-day Bedouins and Saudi rather than to most neighbouring Levantine groups. This study represents the genomic analysis of a secondary use site with characteristics consistent with an early Islamic burial in the Levant. We discuss our findings and possible historic scenarios in the light of forces such as genetic drift and their possible interaction with religious and cultural processes (including diet and subsistence practices)

Gender Differences and the Impact of Partnership and Children on Quality of Life During the COVID-19 Pandemic

Objectives: The COVID-19 pandemic and its protective measures have changed the daily lives of families and may have affected quality of life (QoL). The aim of this study was to analyze gender differences in QoL and to examine individuals living in different partnership and family constellations.Methods: Data from the Gutenberg COVID-19 cohort study (N = 10,250) with two measurement time points during the pandemic (2020 and 2021) were used. QoL was assessed using the EUROHIS-QOL questionnaire. Descriptive analyses and autoregressive regressions were performed.Results: Women reported lower QoL than men, and QoL was significantly lower at the second measurement time point in both men and women. Older age, male gender, no migration background, and higher socioeconomic status, as well as partnership and children (especially in men), were protective factors for QoL. Women living with children under 14 and single mothers reported significantly lower QoL.Conclusion: Partnership and family were protective factors for QoL. However, women with young children and single mothers are vulnerable groups for lower QoL. Support is especially needed for women with young children

Infectious causes of microcephaly: epidemiology, pathogenesis, diagnosis, and management.

Microcephaly is an important sign of neurological malformation and a predictor of future disability. The 2015-16 outbreak of Zika virus and congenital Zika infection brought the world's attention to links between Zika infection and microcephaly. However, Zika virus is only one of the infectious causes of microcephaly and, although the contexts in which they occur vary greatly, all are of concern. In this Review, we summarise important aspects of major congenital infections that can cause microcephaly, and describe the epidemiology, transmission, clinical features, pathogenesis, management, and long-term consequences of these infections. We include infections that cause substantial impairment: cytomegalovirus, herpes simplex virus, rubella virus, Toxoplasma gondii, and Zika virus. We highlight potential issues with classification of microcephaly and show how some infants affected by congenital infection might be missed or incorrectly diagnosed. Although Zika virus has brought the attention of the world to the problem of microcephaly, prevention of all infectious causes of microcephaly and appropriately managing its consequences remain important global public health priorities

Lack of the Delta Subunit of RNA Polymerase Increases Virulence Related Traits of Streptococcus mutans

The delta subunit of the RNA polymerase, RpoE, maintains the transcriptional specificity in Gram-positive bacteria. Lack of RpoE results in massive changes in the transcriptome of the human dental caries pathogen Streptococcus mutans. In this study, we analyzed traits of the ΔrpoE mutant which are important for biofilm formation and interaction with oral microorganisms and human cells and performed a global phenotypic analysis of its physiological functions. The ΔrpoE mutant showed higher self-aggregation compared to the wild type and coaggregated with other oral bacteria and Candida albicans. It formed a biofilm with a different matrix structure and an altered surface attachment. The amount of the cell surface antigens I/II SpaP and the glucosyltransferase GtfB was reduced. The ΔrpoE mutant displayed significantly stronger adhesion to human extracellular matrix components, especially to fibronectin, than the wild type. Its adhesion to human epithelial cells HEp-2 was reduced, probably due to the highly aggregated cell mass. The analysis of 1248 physiological traits using phenotype microarrays showed that the ΔrpoE mutant metabolized a wider spectrum of carbon sources than the wild type and had acquired resistance to antibiotics and inhibitory compounds with various modes of action. The reduced antigenicity, increased aggregation, adherence to fibronection, broader substrate spectrum and increased resistance to antibiotics of the ΔrpoE mutant reveal the physiological potential of S. mutans and show that some of its virulence related traits are increased