Sporadic Creutzfeldt-Jakob disease infected human cerebral organoids retain the original human brain subtype features following transmission to humanized transgenic mice

Human cerebral organoids (COs) are three-dimensional self-organizing cultures of cerebral brain tissue differentiated from induced pluripotent stem cells. We have recently shown that COs are susceptible to infection with different subtypes of Creutzfeldt-Jakob disease (CJD) prions, which in humans cause different manifestations of the disease. The ability to study live human brain tissue infected with different CJD subtypes opens a wide array of possibilities from differentiating mechanisms of cell death and identifying neuronal selective vulnerabilities to testing therapeutics. However, the question remained as to whether the prions generated in the CO model truly represent those in the infecting inoculum. Mouse models expressing human prion protein are commonly used to characterize human prion disease as they reproduce many of the molecular and clinical phenotypes associated with CJD subtypes. We therefore inoculated these mice with COs that had been infected with two CJD subtypes (MV1 and MV2) to see if the original subtype characteristics (referred to as strains once transmitted into a model organism) of the infecting prions were maintained in the COs when compared with the original human brain inocula. We found that disease characteristics caused by the molecular subtype of the disease associated prion protein were similar in mice inoculated with either CO derived material or human brain material, demonstrating that the disease associated prions generated in COs shared strain characteristics with those in humans. As the first and only in vitro model of human neurodegenerative disease that can faithfully reproduce different subtypes of prion disease, these findings support the use of the CO model for investigating human prion diseases and their subtypes

Senior Sway: Using a Mobile Application to Measure Fall Risk

Background and Purpose: The Senior Sway mobile application uses the iPhone/iPad gyroscope to assess postural sway and motion reaction time. Impairment in postural sway and motion reaction time have the potential to increase risk for future falls. Senior Sway thereby has the potential to provide a quick, easy to use, objective measure for predicting falls in older adults. The purpose of this study was to evaluate the feasibility of the Senior Sway mobile application and its associations with fall risk in community-dwelling older adults. Methods: Adults older than 62 years were recruited from senior centers and community events. Descriptive and bivariate statistics were used to examine feasibility on the basis of enrollment, time required, satisfaction with application, and association with fall risk. Results and Discussion: Fifty-seven adults were recruited. Use of the Senior Sway mobile application was feasible. Ninety-one percent said that they liked the application and reported length of time of assessment was “just right.” The average Senior Sway score was 64.0 (range: 47.8-84.0), which was signifi cantly associated with the 30-second sit-to-stand test. In addition, the motor reaction time score was associated with the Timed Up and Go. Conclusions: Senior Sway is a promising application to improve identifi cation of adults at risk for falls and need for rehabilitation but warrants further research

Trauma and posttraumatic stress disorder in South Africa: analysis from the South African Stress and Health Study

Background: South Africa’s unique history, characterised by apartheid, a form of constitutional racial segregation and exploitation, and a long period of political violence and state-sponsored oppression ending only in 1994, suggests a high level of trauma exposure in the general population. The aim of this study was to document the epidemiology of trauma and posttraumatic stress disorder (PTSD) in the South African general population. Methods: The South African Stress and Health Study is a nationally representative survey of South African adults using the WHO’s Composite International Diagnostic Interview (CIDI) to assess exposure to trauma and presence of DSM-IV mental disorders. Results: The most common traumatic events were the unexpected death of a loved one and witnessing trauma occurring to others. Lifetime and 12-month prevalence rates of PTSD were 2.3% and 0.7% respectively, while the conditional prevalence of PTSD after trauma exposure was 3.5%. PTSD conditional risk after trauma exposure and probability of chronicity after PTSD onset were both highest for witnessing trauma. Socio-demographic factors such as sex, age and education were largely unrelated to PTSD risk. Conclusions: The occurrence of trauma and PTSD in South Africa is not distributed according to the sociodemographic factors or trauma types observed in other countries. The dominant role of witnessing in contributing to PTSD may reflect the public settings of trauma exposure in South Africa and highlight the importance of political and social context in shaping the epidemiology of PTSD

Researchers’ perceptions of ethical authorship distribution in collaborative research teams

Authorship is commonly used as the basis for the measurement of research productivity. It influences career progression and rewards, making it a valued commodity in a competitive scientific environment. To better understand authorship practices amongst collaborative teams, this study surveyed authors on collaborative journal articles published between 2011 and 2015. Of the 8364 respondents, 1408 responded to the final open-ended question, which solicited additional comments or remarks regarding the fair distribution of authorship in research teams. This paper presents the analysis of these comments, categorized into four main themes: (1) disagreements, (2) questionable behavior, (3) external influences regarding authorship, and (4) values promoted by researchers. Results suggest that some respondents find ways to effectively manage disagreements in a collegial fashion. Conversely, others explain how distribution of authorship can become a "blood sport" or a "horror story" which can negatively affect researchers' wellbeing, scientific productivity and integrity. Researchers fear authorship discussions and often try to avoid openly discussing the situation which can strain team interactions. Unethical conduct is more likely to result from deceit, favoritism, and questionable mentorship and may become more egregious when there is constant bullying and discrimination. Although values of collegiality, transparency and fairness were promoted by researchers, rank and need for success often overpowered ethical decision-making. This research provides new insight into contextual specificities related to fair authorship distribution that can be instrumental in developing applicable training tools to identify, prevent, and mitigate authorship disagreement

Satellite-based emergency mapping using optical imagery: experience and reflections from the 2015 Nepal earthquakes

Landslides triggered by large earthquakes in mountainous regions contribute significantly to overall earthquake losses and pose a major secondary hazard that can persist for months or years. While scientific investigations of coseismic landsliding are increasingly common, there is no protocol for rapid (hours-to-days) humanitarian-facing landslide assessment and no published recognition of what is possible and what is useful to compile immediately after the event. Drawing on the 2015 Mw 7.8 Gorkha earthquake in Nepal, we consider how quickly a landslide assessment based upon manual satellite-based emergency mapping (SEM) can be realistically achieved and review the decisions taken by analysts to ascertain the timeliness and type of useful information that can be generated. We find that, at present, many forms of landslide assessment are too slow to generate relative to the speed of a humanitarian response, despite increasingly rapid access to high-quality imagery. Importantly, the value of information on landslides evolves rapidly as a disaster response develops, so identifying the purpose, timescales, and end users of a post-earthquake landslide assessment is essential to inform the approach taken. It is clear that discussions are needed on the form and timing of landslide assessments, and how best to present and share this information, before rather than after an earthquake strikes. In this paper, we share the lessons learned from the Gorkha earthquake, with the aim of informing the approach taken by scientists to understand the evolving landslide hazard in future events and the expectations of the humanitarian community involved in disaster response. Please read the corrigendum first before accessing the articl

Role of Secondary Organic Matter on Soot Particle Toxicity in Reconstituted Human Bronchial Epithelia Exposed at the Air-Liquid Interface.

Secondary organic matter (SOM) formed from gaseous precursors constitutes a major mass fraction of fine particulate matter. However, there is only limited evidence on its toxicological impact. In this study, air-liquid interface cultures of human bronchial epithelia were exposed to different series of fresh and aged soot particles generated by a miniCAST burner combined with a micro smog chamber (MSC). Soot cores with geometric mean mobility diameters of 30 and 90 nm were coated with increasing amounts of SOM, generated from the photo-oxidation of mesitylene and ozonolysis of α-pinene. At 24 h after exposure, the release of lactate dehydrogenase (LDH), indicating cell membrane damage, was measured and proteome analysis, i.e. the release of 102 cytokines and chemokines to assess the inflammatory response, was performed. The data indicate that the presence of the SOM coating and its bioavailability play an important role in cytotoxicity. In particular, LDH release increased with increasing SOM mass/total particle mass ratio, but only when SOM had condensed on the outer surface of the soot cores. Proteome analysis provided further evidence for substantial interference of coated particles with essential properties of the respiratory epithelium as a barrier as well as affecting cell remodeling and inflammatory activity

Foveal Curvature and Its Associations in UK Biobank Participants

PURPOSE. To examine whether sociodemographic, and ocular factors relate to optical coherence tomography (OCT)-derived foveal curvature (FC) in healthy individuals. METHODS. We developed a deep learning model to quantify OCT-derived FC from 63, 939 participants (age range, 39-70 years). Associations of FC with sociodemographic, and ocular factors were obtained using multilevel regression analysis (to allow for right and left eyes) adjusting for age, sex, ethnicity, height (model 1), visual acuity, spherical equivalent, corneal astigmatism, center point retinal thickness (CPRT), intraocular pressure (model 2), deprivation (Townsend index), higher education, annual income, and birth order (model 3). Fovea curvature was modeled as a z-score. RESULTS. Males had on average steeper FC (0.077; 95% confidence interval [CI] 0.077-0.078) than females (0.068; 95% CI 0.068-0.069). Compared with whites, non-white individuals showed flatter FC, particularly those of black ethnicity. In black males, -0.80 standard deviation (SD) change when compared with whites (95% CI -0.89, -0.71; P 5.2e10-68). In black females, -0.70 SD change when compared with whites (95% CI -0.77, -0.63; p 2.3e10-93). Ocular factors (visual acuity, refractive status, and CPRT) showed a graded inverse association with FC that persisted after adjustment. Macular curvature showed a positive association with FC. Income showed a linear trend increase in males (P for linear trend = 0.005). CONCLUSIONS. We demonstrate marked differences in FC with ethnicity on the largest cohort studied for this purpose to date. Ocular factors showed a graded association with FC. Implementation of FC quantification in research and on the clinical setting can enhance the understanding of clinical macular phenotypes in health and disease