Consequences of Hyperoxia and the Toxicity of Oxygen in the Lung

Oxygen (O2) is life essential but as a drug has a maximum positive biological benefit and accompanying toxicity effects. Oxygen is therapeutic for treatment of hypoxemia and hypoxia associated with many pathological processes. Pathophysiological processes are associated with increased levels of hyperoxia-induced reactive O2 species (ROS) which may readily react with surrounding biological tissues, damaging lipids, proteins, and nucleic acids. Protective antioxidant defenses can become overwhelmed with ROS leading to oxidative stress. Activated alveolar capillary endothelium is characterized by increased adhesiveness causing accumulation of cell populations such as neutrophils, which are a source of ROS. Increased levels of ROS cause hyperpermeability, coagulopathy, and collagen deposition as well as other irreversible changes occurring within the alveolar space. In hyperoxia, multiple signaling pathways determine the pulmonary cellular response: apoptosis, necrosis, or repair. Understanding the effects of O2 administration is important to prevent inadvertent alveolar damage caused by hyperoxia in patients requiring supplemental oxygenation

NASA Undergraduate Student Instrument Project (USIP) Lessons Learned

NASA offers real-world experiences, with the goal of developing students’ competencies in science, technology, engineering and math (STEM), skills critical to building a STEM-literate workforce and achieving the nation\u27s exploration goals. In 2016, the NASA Science Mission Directorate (SMD) and the Office of Education National Space Grant Program (OE Space Grant) awarded $8 million through the Undergraduate Student Instrument Project (USIP) to 47 student teams to conduct hands-on research with 23 of the projects being CubeSat projects. The USIP student teams proposed science or technology experiments that are relevant to NASA missions, and the platform to fly their payload. The platforms include sounding rockets, scientific and hand-held balloons, aircraft, suborbital reusable and commercial launch vehicles, and CubeSats launched as a secondary payload on an orbital vehicle. The mission management for USIP was the responsibility of NASA Goddard Space Flight Centers Wallops Flight Facility (WFF) in Virginia. The university faculty supporting USIP attest to the benefits students are receiving in the hands-on aspects of the projects, as well as the real-world problem resolution. The USIP university teams are receiving an authentic NASA educational experience that will encourage the students to be part of NASA’s or the Nations’ future workforce and leaders

NASA Undergraduate Student Instrument (USIP) Project--Lessons Learned

NASA offers real-world experiences, with the goal of developing students skills and capabilities in science, technology, engineering and math, skills critical to building a STEM-literate workforce and achieving the nation's exploration goals. In 2016, the NASA Science Mission Directorate (SMD) and the Office of Education National Space Grant Program (OE Space Grant) awarded $8 million through the Undergraduate Student Instrument Project (USIP) to 47 student teams to conduct hands-on research with 23 of the projects being CubeSat projects. The USIP student teams proposed science or technology experiments that are relevant to NASA missions, and the platform to fly their payload. The platforms include sounding rockets, scientific and hand-held balloons, aircraft, suborbital reusable and commercial launch vehicles, and CubeSats launched as a secondary payload on an orbital vehicle. The mission management for USIP was the responsibility of NASA Goddard Space Flight Centers Wallops Flight Facility (WFF) in Virginia. The university faculty supporting USIP attest to the benefits students are receiving in the hands-on aspects of the projects, as well as the real-world problem resolution. The USIP university teams are receiving an authentic NASA educational experience that will encourage the students to be part of NASAs or the Nations future workforce and leaders

Trial and error versus errorless learning of functional skills in patients with acute stroke

Objective: To compare the effectiveness of errorless learning versus trial and error learning for teaching activities of daily living to patients with acute stroke with or without explicit memory impairments. Design: Randomized crossover. Setting: Rehabilitation hospital. Participants: 33 adult subjects following an acute stroke. Intervention: Subjects were taught to prepare a wheelchair for a transfer and to put on a sock with a sock-donner. Tasks were taught using errorless learning or trial and error learning. Explicit memory was assessed using the Neurobehavioral Cognitive Status Exam. Main Outcome Measures: Days until subject was able to demonstrate retention of the task, and success or failure at carry-over to a similar task. Results: No significant differences were found in days to retention for either functional task when taught using errorless learning or trial and error learning in subjects with or without explicit memory impairments. Carry-over was significantly better when trial and error learning was used for learning sock donning. Conclusions: When choosing the best learning method for patients undergoing rehabilitation for stroke, the nature of the task should be considered. Additional research is needed to identify the best approach for teaching activities of daily living and facilitating carry-over of learning in individuals with acute stroke

Topical, geospatial, and temporal diffusion of the 2015 North American Menopause Society position statement on nonhormonal management of vasomotor symptoms

OBJECTIVE: We sought to depict the topical, geospatial, and temporal diffusion of the 2015 North American Menopause Society position statement on the nonhormonal management of menopause-associated vasomotor symptoms released on September 21, 2015, and its associated press release from September 23, 2015. METHODS: Three data sources were used: online news articles, National Public Radio, and Twitter. For topical diffusion, we compared keywords and their frequencies among the position statement, press release, and online news articles. We also created a network figure depicting relationships across key content categories or nodes. For geospatial diffusion within the United States, we compared locations of the 109 National Public Radio (NPR) stations covering the statement to 775 NPR stations not covering the statement. For temporal diffusion, we normalized and segmented Twitter data into periods before and after the press release (September 12, 2015 to September 22, 2015 vs September 23, 2015 to October 3, 2015) and conducted a burst analysis to identify changes in tweets from before to after. RESULTS: Topical information diffused across sources was similar with the exception of the more scientific terms "vasomotor symptoms" or "vms" versus the more colloquial term "hot flashes." Online news articles indicated media coverage of the statement was mainly concentrated in the United States. NPR station data showed similar proportions of stations airing the story across the four census regions (Northeast, Midwest, south, west; P = 0.649). Release of the statement coincided with bursts in the menopause conversation on Twitter. CONCLUSIONS: The findings of this study may be useful for directing the development and dissemination of future North American Menopause Society position statements and/or press releases

Detection of endometrial cancer in cervico-vaginal fluid and blood plasma:leveraging proteomics and machine learning for biomarker discovery

BACKGROUND: The anatomical continuity between the uterine cavity and the lower genital tract allows for the exploitation of uterine-derived biomaterial in cervico-vaginal fluid for endometrial cancer detection based on non-invasive sampling methodologies. Plasma is an attractive biofluid for cancer detection due to its simplicity and ease of collection. In this biomarker discovery study, we aimed to identify proteomic signatures that accurately discriminate endometrial cancer from controls in cervico-vaginal fluid and blood plasma.METHODS: Blood plasma and Delphi Screener-collected cervico-vaginal fluid samples were acquired from symptomatic post-menopausal women with (n = 53) and without (n = 65) endometrial cancer. Digitised proteomic maps were derived for each sample using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning was employed to identify the most discriminatory proteins. The best diagnostic model was determined based on accuracy and model parsimony.FINDINGS: A protein signature derived from cervico-vaginal fluid more accurately discriminated cancer from control samples than one derived from plasma. A 5-biomarker panel of cervico-vaginal fluid derived proteins (HPT, LG3BP, FGA, LY6D and IGHM) predicted endometrial cancer with an AUC of 0.95 (0.91-0.98), sensitivity of 91% (83%-98%), and specificity of 86% (78%-95%). By contrast, a 3-marker panel of plasma proteins (APOD, PSMA7 and HPT) predicted endometrial cancer with an AUC of 0.87 (0.81-0.93), sensitivity of 75% (64%-86%), and specificity of 84% (75%-93%). The parsimonious model AUC values for detection of stage I endometrial cancer in cervico-vaginal fluid and blood plasma were 0.92 (0.87-0.97) and 0.88 (0.82-0.95) respectively.INTERPRETATION: Here, we leveraged the natural shed of endometrial tumours to potentially develop an innovative approach to endometrial cancer detection. We show proof of principle that endometrial cancers secrete unique protein signatures that can enable cancer detection via cervico-vaginal fluid assays. Confirmation in a larger independent cohort is warranted.FUNDING: Cancer Research UK, Blood Cancer UK, National Institute for Health Research.</p

Detection of endometrial cancer in cervico-vaginal fluid and blood plasma:leveraging proteomics and machine learning for biomarker discovery

BACKGROUND: The anatomical continuity between the uterine cavity and the lower genital tract allows for the exploitation of uterine-derived biomaterial in cervico-vaginal fluid for endometrial cancer detection based on non-invasive sampling methodologies. Plasma is an attractive biofluid for cancer detection due to its simplicity and ease of collection. In this biomarker discovery study, we aimed to identify proteomic signatures that accurately discriminate endometrial cancer from controls in cervico-vaginal fluid and blood plasma.METHODS: Blood plasma and Delphi Screener-collected cervico-vaginal fluid samples were acquired from symptomatic post-menopausal women with (n = 53) and without (n = 65) endometrial cancer. Digitised proteomic maps were derived for each sample using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning was employed to identify the most discriminatory proteins. The best diagnostic model was determined based on accuracy and model parsimony.FINDINGS: A protein signature derived from cervico-vaginal fluid more accurately discriminated cancer from control samples than one derived from plasma. A 5-biomarker panel of cervico-vaginal fluid derived proteins (HPT, LG3BP, FGA, LY6D and IGHM) predicted endometrial cancer with an AUC of 0.95 (0.91-0.98), sensitivity of 91% (83%-98%), and specificity of 86% (78%-95%). By contrast, a 3-marker panel of plasma proteins (APOD, PSMA7 and HPT) predicted endometrial cancer with an AUC of 0.87 (0.81-0.93), sensitivity of 75% (64%-86%), and specificity of 84% (75%-93%). The parsimonious model AUC values for detection of stage I endometrial cancer in cervico-vaginal fluid and blood plasma were 0.92 (0.87-0.97) and 0.88 (0.82-0.95) respectively.INTERPRETATION: Here, we leveraged the natural shed of endometrial tumours to potentially develop an innovative approach to endometrial cancer detection. We show proof of principle that endometrial cancers secrete unique protein signatures that can enable cancer detection via cervico-vaginal fluid assays. Confirmation in a larger independent cohort is warranted.FUNDING: Cancer Research UK, Blood Cancer UK, National Institute for Health Research.</p

COVID-19 and children

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in transmission, especially in schools and at home, is crucial to ensuring effective mitigation measures. Therefore, in addition to nonpharmaceutical interventions, such as improved ventilation, there is a strong case to vaccinate children so as to reduce possible long-term effects from infection and to decrease transmission. But questions remain about whether vaccination might skew immune responses to variants in the long term. As the experts discuss below, more is being learned about these important issues, but much more research is needed to understand the long-term effects of COVID-19 in children

Climate and Landscape Factors Associated with Buruli Ulcer Incidence in Victoria, Australia

Background Buruli ulcer (BU), caused by Mycobacterium ulcerans (M. ulcerans), is a necrotizing skin disease found in more than 30 countries worldwide. BU incidence is highest in West Africa; however, cases have substantially increased in coastal regions of southern Australia over the past 30 years. Although the mode of transmission remains uncertain, the spatial pattern of BU emergence in recent years seems to suggest that there is an environmental niche for M. ulcerans and BU prevalence. Methodology/Principal Findings Network analysis was applied to BU cases in Victoria, Australia, from 1981–2008. Results revealed a non-random spatio-temporal pattern at the regional scale as well as a stable and efficient BU disease network, indicating that deterministic factors influence the occurrence of this disease. Monthly BU incidence reported by locality was analyzed with landscape and climate data using a multilevel Poisson regression approach. The results suggest the highest BU risk areas occur at low elevations with forested land cover, similar to previous studies of BU risk in West Africa. Additionally, climate conditions as far as 1.5 years in advance appear to impact disease incidence. Warmer and wetter conditions 18–19 months prior to case emergence, followed by a dry period approximately 5 months prior to case emergence seem to favor the occurrence of BU. Conclusions/Significance The BU network structure in Victoria, Australia, suggests external environmental factors favor M. ulcerans transmission and, therefore, BU incidence. A unique combination of environmental conditions, including land cover type, temperature and a wet-dry sequence, may produce habitat characteristics that support M. ulcerans transmission and BU prevalence. These findings imply that future BU research efforts on transmission mechanisms should focus on potential vectors/reservoirs found in those environmental niches. Further, this study is the first to quantitatively estimate environmental lag times associated with BU outbreaks, providing insights for future transmission investigations.This project was supported by the World Health Organization and the National Institutes of Health and Fogarty International Center (NIH - R01TW007550). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Fogarty International Center or the National Institutes of Health. R.W. Merritt is gratefully acknowledged for supporting this research as part of NIH grant R01TW007550