Offering Hope and Making Attributions through YouTube: An Exploratory Ethnographic Content Analysis of the Social Change-Oriented “It Gets Better Project”

In response to multiple youth suicides, Dan Savage and Terry Miller founded a YouTube channel that later became the It Gets Better Project (IGBP). The ever-growing corpus of IGBP videos now includes over 50,000 “messages of hope” targeting at-risk LGBTQ and questioning youth. Employing Ethnographic Content Analysis (ECA) and the theoretical lens of attribution, this study offers insight into how LGBTQ bullying and harassment are discussed in the IGBP and to what they are internally and externally attributed. Findings revealed external attributions were more prevalent than internal attributions pertaining to types of harassment and bullying experienced as well as explanations of how “it gets better,” with a focus on institutions as both the cause of and remedy for bullying and harassment

Relationship between negative emotions and perceived support among parents of hospitalized, critically ill children.

Objectives: The purpose of this study was to describe relationships between negative emotions and perceived emotional support in parents of children admitted to the pediatric intensive care unit (PICU). Methods: This cross-sectional descriptive study conducted face-to-face interviews between January 2019 and January 2020. Study variables included depression (PHQ-9 Scale), anxiety (Emotional Distress-Anxiety-Short Form 8a), anger (Emotional Distress-Anger-Short Form 5a), fear (Fear-Affect Computerized Adaptive Test), somatic fear (Fear-Somatic Arousal-Fixed Form), loneliness (Revised 20-item UCLA Loneliness Scale), and perceived emotional support (Emotional Support-Fixed Form). Results: Eighty parents reported symptoms of depression 8.00(4.00, 13.75), anxiety (23.43 ± 7.80), anger (13.40 ± 5.46), fear (72.81 ± 27.26), somatic fear 9.00(6.00, 12.75), loneliness (39.35 ± 12.00), and low perceived emotional support (32.14 ± 8.06). Parents who were young, single, low-income, and with limited-post secondary education reported greater loneliness and lower perceived emotional support. Fear correlated with depression ( Conclusions: The cluster of negative emotions identified will serve as potential targets for future interventions designed to enhance support for parents of critically ill children

Reversible oligonucleotide chain blocking enables bead capture and amplification of T-Cell receptor alpha and beta chain mRNAs

Next-generation sequencing (NGS) has proven to be an exceptionally powerful tool for studying genetic variation and differences in gene expression profiles between cell populations. However, these population-wide studies are limited by their inability to detect variation between individual cells within a population, inspiring the development of single-cell techniques such as Drop-seq, which add a unique barcode to the mRNA from each cell prior to sequencing. Current Drop-seq technology enables capture, amplification, and barcoding of the entire mRNA transcriptome of individual cells. NGS can then be used to sequence the 3′-end of each message to build a cell-specific transcriptional landscape. However, current technology does not allow high-throughput capture of information distant from the mRNA poly-A tail. Thus, gene profiling would have much greater utility if beads could be generated having multiple transcript-specific capture sequences. Here we report the use of a reversible chain blocking group to enable synthesis of DNA barcoded beads having capture sequences for the constant domains of the T-cell receptor α and β chain mRNAs. We demonstrate that these beads can be used to capture and pair TCRα and TCRβ sequences from total T-cell RNA, enabling reverse transcription and PCR amplification of these sequences. This is the first example of capture beads having more than one capture sequence, and we envision that this technology will be of high utility for applications such as pairing the antigen receptor chains that give rise to autoimmune diseases or measuring the ratios of mRNA splice variants in cancer stem cells

Cognitive tests used in chronic adult human randomised controlled trial micronutrient and phytochemical intervention studies

In recent years there has been a rapid growth of interest in exploring the relationship between nutritional therapies and the maintenance of cognitive function in adulthood. Emerging evidence reveals an increasingly complex picture with respect to the benefits of various food constituents on learning, memory and psychomotor function in adults. However, to date, there has been little consensus in human studies on the range of cognitive domains to be tested or the particular tests to be employed. To illustrate the potential difficulties that this poses, we conducted a systematic review of existing human adult randomised controlled trial (RCT) studies that have investigated the effects of 24 d to 36 months of supplementation with flavonoids and micronutrients on cognitive performance. There were thirty-nine studies employing a total of 121 different cognitive tasks that met the criteria for inclusion. Results showed that less than half of these studies reported positive effects of treatment, with some important cognitive domains either under-represented or not explored at all. Although there was some evidence of sensitivity to nutritional supplementation in a number of domains (for example, executive function, spatial working memory), interpretation is currently difficult given the prevailing 'scattergun approach' for selecting cognitive tests. Specifically, the practice means that it is often difficult to distinguish between a boundary condition for a particular nutrient and a lack of task sensitivity. We argue that for significant future progress to be made, researchers need to pay much closer attention to existing human RCT and animal data, as well as to more basic issues surrounding task sensitivity, statistical power and type I error

NASA's Functional Task Test: High Intensity Exercise Improves the Heart Rate Response to a Stand Test Following 70 Days of Bedrest

Cardiovascular adaptations due to spaceflight are modeled with 6deg head-down tilt bed rest (BR) and result in decreased orthostatic tolerance. We investigated if high-intensity resistive and aerobic exercise with and without testosterone supplementation would improve the heart rate (HR) response to a 3.5-min stand test and how quickly these changes recovered following BR. During 70 days of BR male subjects performed no exercise (Control, n=10), high intensity supine resistive and aerobic exercise (Exercise, n=9), or supine exercise plus supplemental testosterone (Exercise+T, n=8; 100 mg i.m., weekly in 2-week on/off cycles). We measured HR for 2 min while subjects were prone and for 3 min after standing twice before and 0, 1, 6, and 11 days after BR. Mixed-effects linear regression models were used to evaluate group, time, and interaction effects. Compared to pre-bed rest, prone HR was elevated on BR+0 and BR+1 in Control, but not Exercise or Exercise+T groups, and standing HR was greater in all 3 groups. The increase in prone and standing HR in Control subjects was greater than either Exercise or Exercise+T groups and all groups recovered by BR+6. The change in HR from prone to standing more than doubled on BR+0 in all groups, but was significantly less in the Exericse+T group compared to the Control, but not Exercise group. Exercise reduces, but does not prevent the increase in HR observed in response to standing. The significantly lower HR response in the Exercise+T group requires further investigation to determine physiologic significance

Hemozoin produced by mammals confers heme tolerance

Free heme is cytotoxic as exemplified by hemolytic diseases and genetic deficiencies in heme recycling and detoxifying pathways. Thus, intracellular accumulation of heme has not been observed in mammalian cells to date. Here we show that mice deficient for the heme transporter SLC48A1 (also known as HRG1) accumulate over ten-fold excess heme in reticuloendothelial macrophage lysosomes that are 10 to 100 times larger than normal. Macrophages tolerate these high concentrations of heme by crystallizing them into hemozoin, which heretofore has only been found in blood-feeding organisms. SLC48A1 deficiency results in impaired erythroid maturation and an inability to systemically respond to iron deficiency. Complete heme tolerance requires a fully-operational heme degradation pathway as haplo insufficiency of HMOX1 combined with SLC48A1 inactivation causes perinatal lethality demonstrating synthetic lethal interactions between heme transport and degradation. Our studies establish the formation of hemozoin by mammals as a previously unsuspected heme tolerance pathway

Effect of 1% Inspired CO2 During Head-Down Tilt on Ocular Structures, Cerebral Blood Flow, and Visual Acuity in Healthy Human Subjects

The cephalad fluid shift induced by microgravity has been hypothesized to elevate intracranial pressure (ICP) and contribute to the development of the visual impairment/intracranial pressure (VIIP) syndrome experienced by many astronauts during and after long-duration space flight. In addition, elevated ambient partial pressure of carbon dioxide (PCO2) on the International Space Station (ISS) has also been hypothesized to contribute to the development of VIIP. We seek to determine if an acute, mild CO2 exposure, similar to that occurring on the ISS, combined with the cephalad fluid shift induced by head-down tilt will induce ophthalmic and ICP changes consistent with the VIIP syndrome

Insertion of a Synthetic Switch Into Insulin Provides Metabolite-Dependent Regulation of Hormone-Receptor Activation

Insulin signaling requires conformational change: whereas the free hormone and its receptor each adopt autoinhibited conformations, their binding leads to large-scale structural reorganization. To test the coupling between insulin’s “opening” and receptor activation, we inserted an artificial ligand-dependent switch into insulin. Ligand binding disrupts an internal tether designed to stabilize the hormone’s native closed and inactive conformation, thereby enabling productive receptor engagement. This scheme exploited a diol sensor (meta-fluoro-phenylboronic acid at GlyA1) and internal diol (3,4-dihydroxybenzoate at LysB28). The sensor recognizes monosaccharides (fructose > glucose). Studies of insulin signaling in human hepatoma-derived cells (HepG2) demonstrated fructose-dependent receptor autophosphorylation leading to appropriate downstream signaling events, including a specific kinase cascade and metabolic gene regulation (gluconeogenesis and lipogenesis). Addition of glucose (an isomeric ligand with negligible sensor affinity) did not activate the receptor. Similarly, metabolite-regulated signaling was not observed in control studies of (i) an unmodified insulin analog or (ii) an analog containing a diol sensor in the absence of internal tethering. Although as expected CD-detected secondary structure was unaffected by ligand binding, heteronuclear NMR studies revealed subtle local and nonlocal monosaccharide-dependent changes in structure. Insertion of a synthetic switch into insulin has thus demonstrated coupling between hinge-opening and holoreceptor signaling. In addition to this basic finding, our results provide proof of principle for a mechanism-based metabolite-responsive insulin. In particular, replacement of the present fructose sensor by an analogous glucose sensor may enable translational development of a “smart” insulin analog designed to mitigate risk of hypoglycemia in the treatment of diabetes mellitus

Pilot Field Test: Results of Tandem Walk Performance Following Long-Duration Spaceflight

Coordinated locomotion has proven to be challenging for many astronauts following long duration spaceflight. As NASA's vision for spaceflight points toward interplanetary travel and missions to distant objects, astronauts will not have assistance once they land. Thus, it is vital to develop a knowledge base from which operational guidelines can be written that define when astronauts can be expected to safely perform certain tasks. Data obtained during the Field Test experiment will add important insight to this knowledge base. Specifically, we aim to develop a recovery timeline of functional sensorimotor performance during the first 24 hours and several days after landing. A forerunner of the full Field Test study, the Pilot Field Test (PFT) comprised a subset of the tasks and measurements to be included in the ultimate set