Submacular Choroid Thickness Increases During Long-Duration Spaceflight

The Spaceflight Associated Neuro-ocular Syndrome (SANS) is characterized by the development of optic disc edema, choroidal folds, cotton-wool spots, globe flattening, and/or refractive error changes greater than or equal to 0.75D during long-duration spaceflight to the International Space Station (ISS). It is hypothesized that these findings result from the headward fluid shift that occurs due to weightlessness. We can induce a headward fluid shift on Earth using positional changes and on ISS due to weightlessness. Lower-body negative pressure (LBNP) is used to reverse the headward fluid shift by drawing fluid into the lower body and can be used on Earth and on ISS

New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Current practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer patients with tumor-involved sentinel lymph nodes (SLNs), although fewer than half will have non-sentinel node (NSLN) metastasis. Our goal was to develop new models to quantify the risk of NSLN metastasis in SLN-positive patients and to compare predictive capabilities to another widely used model.</p> <p>Methods</p> <p>We constructed three models to predict NSLN status: recursive partitioning with receiver operating characteristic curves (RP-ROC), boosted Classification and Regression Trees (CART), and multivariate logistic regression (MLR) informed by CART. Data were compiled from a multicenter Northern California and Oregon database of 784 patients who prospectively underwent SLN biopsy and completion ALND. We compared the predictive abilities of our best model and the Memorial Sloan-Kettering Breast Cancer Nomogram (Nomogram) in our dataset and an independent dataset from Northwestern University.</p> <p>Results</p> <p>285 patients had positive SLNs, of which 213 had known angiolymphatic invasion status and 171 had complete pathologic data including hormone receptor status. 264 (93%) patients had limited SLN disease (micrometastasis, 70%, or isolated tumor cells, 23%). 101 (35%) of all SLN-positive patients had tumor-involved NSLNs. Three variables (tumor size, angiolymphatic invasion, and SLN metastasis size) predicted risk in all our models. RP-ROC and boosted CART stratified patients into four risk levels. MLR informed by CART was most accurate. Using two composite predictors calculated from three variables, MLR informed by CART was more accurate than the Nomogram computed using eight predictors. In our dataset, area under ROC curve (AUC) was 0.83/0.85 for MLR (n = 213/n = 171) and 0.77 for Nomogram (n = 171). When applied to an independent dataset (n = 77), AUC was 0.74 for our model and 0.62 for Nomogram. The composite predictors in our model were the product of angiolymphatic invasion and size of SLN metastasis, and the product of tumor size and square of SLN metastasis size.</p> <p>Conclusion</p> <p>We present a new model developed from a community-based SLN database that uses only three rather than eight variables to achieve higher accuracy than the Nomogram for predicting NSLN status in two different datasets. </p

Tissue engineering of the naturally-derived scaffold with adjustable mechanical properties, modified surface chemistry, and interconnected pores

Less than half of patients have chronic diseases, but their treatment accounts for over 75% of healthcare spending. Regeneration and replacement strategies are the only long-term treatment options for many chronic diseases. The success of tissue regeneration and replacement methods depends upon the development of scaffolds that mimic the native extracellular matrix, support the growth and organization of cells into tissue, and integrate properly with host tissue. The naturally-derived scaffold is made of demineralized cancellous bone which is a strong but flexible, porous material composed primarily of Type I collagen. Since the scaffold can be derived from varying cancellous bone sources, characterization of site differences has the potential to further inform scaffold design. Mechanical characterization of site differences and crosslinking involved compressive and tensile testing as well as permeability and degradation experiments. Proper cell interactions and nutrient transport are primary scaffold requirements that were also investigated. The surface chemistry of the naturally-derived scaffold was altered to promote specific cell interactions. Additionally, the naturally-derived scaffold can provide mechanical support for polymer gels. With adjustable mechanical properties and tunable cell interactions along with the option to accommodate polymer gel strategies, the scaffold has the potential to support diverse tissue engineering goals. This research has laid the foundation for continued work in the specific applications of blood vessel and liver replacement to address common chronic diseases such as atherosclerosis and cirrhosis

Data Integration for Health and Stress Monitoring: Biological Metabolites, Wearables Data, and Self-Reporting

Integrative and unobtrusive approaches to monitoring health and stress can assist in preventative medicine and disease management, and provide capabilities for complex work environments, such as military deployments and long-duration human space exploration missions. With many data streams that could potentially provide critical information about the health, behavior, and psychosocial states of individuals or small groups, the central question of this research is how to reliably measure health and stress states over time. This integrative approach to health and stress monitoring has implemented biological metabolite profiling, wearables data analysis, and survey assessment for comparing biological, behavioral, and psychological perspectives. Health monitoring technologies aim to provide objective data about health status. Providing objective information can help mitigate biases or blind spots in an individual’s perception. Consider an individual who is unwilling to openly admit to psychosocial distress and unhealthy habits, or an individual who has habituated to long-term stressors and is unable to recognize a chronic state of high stress. Both honesty and self-awareness are required for accurate self-reporting. Digital health technologies, such as wearable devices, provide objective data for health monitoring. Compared to surveys, wearables are less influenced by participant openness, and compared to biological samples, wearables require less equipment and less labor for analysis. However, inherent to every data stream are limitations due to uncertainty and sensitivity. This research has been conducted in collaboration with Hawaii Space Exploration Analog and Simulation (HI-SEAS), which is a Mars analog research site on the slopes on Mauna Loa volcano in Hawaii. During 8-month and 12-month HI-SEAS missions in the 2014-2016 timeframe, twelve individuals provided hair and urine samples for metabolite profiling, utilized consumer-grade wearables to monitor sleep and activity behaviors, and responded to surveys for recording perceived health and stress levels. This work has developed a self-report instrument for stress characterization, efficient protocols for metabolite profiling, novel measures of sleep quality and activity levels, and has evaluated performance differences of Jawbone® and Fitbit® wearable devices that were worn in tandem. There is considerable debate about the accuracy of data collected from wearable devices. Therefore, the success of next-generation wearable devices is hinging on the ability to reliably process wearables data into meaningful health information. By simultaneously quantifying biological metabolites, sleep and activity behaviors, and psychological perceptions of health, this research is evaluating possible predictors of health and stress, such as evaluating if activity and sleep behaviors recorded by wearables can be predictive of biological metabolites and perceived health. This research has developed data-driven insights for advancing the next-generation of biological, behavioral, and psychological health monitoring capabilities

Development of off-the-shelf hematopoietic stem cell-engineered invariant natural killer T cells for COVID-19 therapeutic intervention.

BackgroundNew COVID-19 treatments are desperately needed as case numbers continue to rise and emergent strains threaten vaccine efficacy. Cell therapy has revolutionized cancer treatment and holds much promise in combatting infectious disease, including COVID-19. Invariant natural killer T (iNKT) cells are a rare subset of T cells with potent antiviral and immunoregulatory functions and an excellent safety profile. Current iNKT cell strategies are hindered by the extremely low presence of iNKT cells, and we have developed a platform to overcome this critical limitation.MethodsWe produced allogeneic HSC-engineered iNKT (AlloHSC-iNKT) cells through TCR engineering of human cord blood CD34+ hematopoietic stem cells (HSCs) and differentiation of these HSCs into iNKT cells in an Ex Vivo HSC-Derived iNKT Cell Culture. We then established in vitro SARS-CoV-2 infection assays to assess AlloHSC-iNKT cell antiviral and anti-hyperinflammation functions. Lastly, using in vitro and in vivo preclinical models, we evaluated AlloHSC-iNKT cell safety and immunogenicity for off-the-shelf application.ResultsWe reliably generated AlloHSC-iNKT cells at high-yield and of high-purity; these resulting cells closely resembled endogenous human iNKT cells in phenotypes and functionalities. In cell culture, AlloHSC-iNKT cells directly killed SARS-CoV-2 infected cells and also selectively eliminated SARS-CoV-2 infection-stimulated inflammatory monocytes. In an in vitro mixed lymphocyte reaction (MLR) assay and an NSG mouse xenograft model, AlloHSC-iNKT cells were resistant to T cell-mediated alloreaction and did not cause GvHD.ConclusionsHere, we report a method to robustly produce therapeutic levels of AlloHSC-iNKT cells. Preclinical studies showed that these AlloHSC-iNKT cells closely resembled endogenous human iNKT cells, could reduce SARS-CoV-2 virus infection load and mitigate virus infection-induced hyperinflammation, and meanwhile were free of GvHD-risk and resistant to T cell-mediated allorejection. These results support the development of AlloHSC-iNKT cells as a promising off-the-shelf cell product for treating COVID-19; such a cell product has the potential to target the new emerging SARS-CoV-2 variants as well as the future new emerging viruses

Working with mental health problems: clients' experiences of IPS, vocational rehabilitation and employment

Background Although the effectiveness of individual placement and support (IPS) has been well established, little is known about clients' perceptions of the model compared to usual vocational rehabilitation, nor about their experiences of searching for and returning to work with this kind of support. This qualitative study aimed to explore clients' views of the difficulties of obtaining and maintaining employment, their experiences of the support received from their IPS or Vocational Service workers and the perceived impact of work on clients' lives. Method Semi-structured interviews were conducted with 48 people with psychotic disorders participating in a six-centre international randomised controlled trial of IPS compared to usual vocational rehabilitation. To assess their experiences of the services and the perceived effects of working, two IPS and two Vocational Service clients at each centre who had found work during the study period were interviewed, along with two IPS and two Vocational Service clients at each centre who had not. Results IPS clients reported having received more help seeking and maintaining employment, whereas Vocational Service clients reported having received more help in finding sheltered employment or placements. Clients who had worked associated this with financial stability, improved social lives, increased self-esteem, integration into society and amelioration of their symptoms, as well as reduced feelings of boredom and isolation, but also reported increased levels of stress. IPS clients as well as Vocational Service ones reported not receiving enough follow-up support, despite this being proposed as a key feature of the model. Conclusion Findings from the in-depth interviews reflect differences in service models that have also been tested quantitatively but further work in disaggregating the IPS model and assessing the impact of each component would be valuable

The Male-Produced Aggregation-Sex Pheromone of the Cerambycid Beetle Plagionotus detritus ssp. detritus

The number of longhorn beetles with confirmed aggregation-sex pheromones has increased rapidly in recent years. However, the species that have been studied most intensively are pests, whereas much less is known about the pheromones of longhorn beetles that are rare or threatened. We studied the cerambycid beetle Plagionotus detritus ssp. detritus with the goal of confirming the presence and composition of an aggregation-sex pheromone. This species has suffered widespread population decline due to habitat loss in Western Europe, and it is now considered threatened and near extinction in several countries. Beetles from a captive breeding program in Sweden were used for headspace sampling. Gas chromatography-mass spectrometry revealed that collections from males contained large quantities of two compounds, identified as (R)-3-hydroxy-2-hexanone (major component) and (S)-2-hydroxy-3-octanone (minor component), in addition to smaller quantities of 2,3-hexanedione and 2,3-octanedione. None of the compounds was present in collections from females. When tested singly in a field bioassay, racemic 3-hydroxy-2-hexanone and 2-hydroxy-3-octanone were not attractive to P. detritus, whereas a 5:1 blend elicited significant attraction. Both compounds are known as components of the pheromones of conspecific beetles, but, to our knowledge, this is the first cerambycid shown to use two compounds with different chain lengths, in which the positions of the hydroxyl and carbonyl functions are interchanged between the two. The pheromone has potential as an efficient tool to detect and monitor populations of P. detritus, and may also be useful in more complex studies on the ecology and conservation requirements of this species