The differential hormonal milieu of morning versus evening, may have an impact on muscle hypertrophic potential

Substantial gains in muscle strength and hypertrophy are clearly associated with the routine performance of resistance training. What is less evident is the optimal timing of the resistance training stimulus to elicit these significant functional and structural skeletal muscle changes. Therefore, this investigation determined the impact of a single bout of resistance training performed either in the morning or evening upon acute anabolic signalling (insulin-like growth factor-binding protein-3 (IGFBP-3), myogenic index and differentiation) and catabolic processes (cortisol). Twenty-four male participants (age 21.4±1.9yrs, mass 83.7±13.7kg) with no sustained resistance training experience were allocated to a resistance exercise group (REP). Sixteen of the 24 participants were randomly selected to perform an additional non-exercising control group (CP) protocol. REP performed two bouts of resistance exercise (80% 1RM) in the morning (AM: 0800 hrs) and evening (PM: 1800 hrs), with the sessions separated by a minimum of 72 hours. Venous blood was collected immediately prior to, and 5 min after, each resistance exercise and control sessions. Serum cortisol and IGFBP-3 levels, myogenic index, myotube width, were determined at each sampling period. All data are reported as mean ± SEM, statistical significance was set at P≤0.05. As expected a significant reduction in evening cortisol concentration was observed at pre (AM: 98.4±10.5, PM: 49.8±4.4 ng/ml, P0.05). Timing of resistance training regimen in the evening appears to augment some markers of hypertrophic potential, with elevated IGFBP-3, suppressed cortisol and a superior cellular environment. Further investigation, to further elucidate the time course of peak anabolic signalling in morning vs evening training conditions, are timely

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

R.: The effects of fully immersive virtual reality on the learning of physical tasks

Fully immersive virtual settings are different from traditional virtual reality settings in that they are able to capture full body motion. This ability allows people to use their full range of physical motion to interact with other avatars, computer controlled agents, and objects in the virtual environment. As such, fully immersive virtual reality presents a novel mediated learning environment in which people can learn physical activities. Capturing human motion for virtual settings has traditionally been a modelbased approach where a few degrees (on the order of tens) of freedom are mapped to virtual model. In contrast, we use an image-based solution that sacrifices visual fidelity for motion fidelity and increased degrees of freedom (on the order of hundreds). Due to the difficulties involved with building suc

Sequential Acute Courses of Transcranial Magnetic Stimulation in Major Depressive Disorder: A Retrospective Analysis in a Veteran Cohort

Background: Repetitive transcranial magnetic stimulation (TMS) is now widely accepted as an effective non-pharmacologic treatment for treatment-resistant depression. However, whether repeated acute TMS courses can recapture the antidepressant effects of the initial acute course is still an open question, especially in the Veteran population. We present here a retrospective analysis of a specialty clinic within the Veteran Affairs Hospital System to help address this question. Aims: Following an acute treatment course of TMS, we sought to determine the treatment response of a subsequent TMS course. We hypothesized that those who responded to an initial acute TMS course would respond in a similar manner to a subsequent treatment course. Methods: 116 cases referred for evaluation for TMS between September 2017 to April 2021 were reviewed. 63 Veterans completed at least one acute course of TMS and 12 completed at least two courses and met inclusion criteria for this review. 6 met criteria for treatment response in the first course, while the other 6 were initial treatment nonresponders. Symptoms were evaluated via self-reported scales at baseline and weekly throughout treatment. Clinical response to subsequent treatment (>50% symptom reduction as measured by the PHQ-9) was compared to initial treatment response. Results: Of the initial treatment responders (n = 6), all six responded to a second acute course, with an 85.3% symptom reduction. Of the initial treatment nonresponders (n = 6), three responded to a second acute course. No adverse events were reported in those who completed a second course, and the Veterans tolerated the treatment well. Conclusions: Our findings support the growing understanding that a second acute TMS treatment course for treatment-resistant depression is safe, well-tolerated, and effective in initial responders and some non-responders. Despite multiple confounders in a naturalistic setting, robust initial treatment response was sustained in a second acute course. Low power limits generalizability, and larger powered, prospective studies are needed

Node-pore sensing enables label-free surface-marker profiling of single cells.

Flow cytometry is a ubiquitous, multiparametric method for characterizing cellular populations. However, this method can grow increasingly complex with the number of proteins that need to be screened simultaneously: spectral emission overlap of fluorophores and the subsequent need for compensation, lengthy sample preparation, and multiple control tests that need to be performed separately must all be considered. These factors lead to increased costs, and consequently, flow cytometry is performed in core facilities with a dedicated technician operating the instrument. Here, we describe a low-cost, label-free microfluidic method that can determine the phenotypic profiles of single cells. Our method employs Node-Pore Sensing to measure the transit times of cells as they interact with a series of different antibodies, each corresponding to a specific cell-surface antigen, that have been functionalized in a single microfluidic channel. We demonstrate the capabilities of our method not only by screening two acute promyelocytic leukemia human cells lines (NB4 and AP-1060) for myeloid antigens, CD13, CD14, CD15, and CD33, simultaneously, but also by distinguishing a mixture of cells of similar size—AP-1060 and NALM-1—based on surface markers CD13 and HLA-DR. Furthermore, we show that our method can screen complex subpopulations in clinical samples: we successfully identified the blast population in primary human bone marrow samples from patients with acute myeloid leukemia and screened these cells for CD13, CD34, and HLA-DR. We show that our label-free method is an affordable, highly sensitive, and user-friendly technology that has the potential to transform cellular screening at the benchside

PBPK model reporting template for chemical risk assessment applications

Physiologically-based pharmacokinetic (PBPK) modeling analysis does not stand on its own for regulatory purposes but is a robust tool to support drug/chemical safety assessment. While the development of PBPK models have grown steadily since their emergence, only a handful of models have been accepted to support regulatory purposes due to obstacles such as the lack of a standardized template for reporting PBPK analysis. Here, we expand the existing guidances designed for pharmaceutical applications by recommending additional elements that are relevant to environmental chemicals. This harmonized reporting template can be adopted and customized by public health agencies receiving PBPK model submission, and it can also serve as general guidance for submitting PBPK-related studies for publication in journals or other modeling sharing purposes. The current effort represents one of several ongoing collaborations among the PBPK modeling and risk assessment communities to promote, when appropriate, incorporating PBPK modeling to characterize the influence of pharmacokinetics on safety decisions made by regulatory agencies.JRC.F.3-Chemicals Safety and Alternative Method

MASTR-MS: a web-based collaborative laboratory information management system (LIMS) for metabolomics

BackgroundAn increasing number of research laboratories and core analytical facilities around the world are developing high throughput metabolomic analytical and data processing pipelines that are capable of handling hundreds to thousands of individual samples per year, often over multiple projects, collaborations and sample types. At present, there are no Laboratory Information Management Systems (LIMS) that are specifically tailored for metabolomics laboratories that are capable of tracking samples and associated metadata from the beginning to the end of an experiment, including data processing and archiving, and which are also suitable for use in large institutional core facilities or multi-laboratory consortia as well as single laboratory environments.ResultsHere we present MASTR-MS, a downloadable and installable LIMS solution that can be deployed either within a single laboratory or used to link workflows across a multisite network. It comprises a Node Management System that can be used to link and manage projects across one or multiple collaborating laboratories; a User Management System which defines different user groups and privileges of users; a Quote Management System where client quotes are managed; a Project Management System in which metadata is stored and all aspects of project management, including experimental setup, sample tracking and instrument analysis, are defined, and a Data Management System that allows the automatic capture and storage of raw and processed data from the analytical instruments to the LIMS.ConclusionMASTR-MS is a comprehensive LIMS solution specifically designed for metabolomics. It captures the entire lifecycle of a sample starting from project and experiment design to sample analysis, data capture and storage. It acts as an electronic notebook, facilitating project management within a single laboratory or a multi-node collaborative environment. This software is being developed in close consultation with members of the metabolomics research community. It is freely available under the GNU GPL v3 licence and can be accessed from, https://muccg.github.io/mastr-ms/