Galvanic vestibular stimulation produces cross-modal improvements in visual thresholds

Background: Stochastic resonance (SR) refers to a faint signal being enhanced with the addition of white noise. Previous studies have found that vestibular perceptual thresholds are lowered with noisy galvanic vestibular stimulation (i.e., "in-channel" SR). Auditory white noise has been shown to improve tactile and visual thresholds, suggesting "cross-modal" SR. Objective: We aimed to study the cross-modal impact of noisy galvanic vestibular stimulation (nGVS) (n=9 subjects) on visual and auditory thresholds. Methods: We measured auditory and visual perceptual thresholds of human subjects across a swath of different nGVS levels in order to determine if a subject-specific best nGVS level elicited a reduction in thresholds as compared the no noise condition (sham). Results: We found an 18% improvement in visual thresholds (p = 0.026). Among the 7 of 9 subjects with reduced thresholds, the average improvement was 26%. Subjects with higher (worse) visual thresholds with no stimulation (sham) improved more than those with lower thresholds (p = 0.005). Auditory thresholds were unchanged by vestibular stimulation. Conclusions: These results are the first demonstration of cross-modal improvement with nGVS, indicating galvanic vestibular white noise can produce cross-modal improvements in some sensory channels, but not all.Comment: 15 pages, 7 figure

Intraocular Pressure and Cardiovascular Alterations Investigated in Artificial Gravity as a Countermeasure to Spaceflight Associated Neuro-ocular Syndrome

Artificial gravity (AG) has been proposed as a countermeasure to spaceflight associated neuro-ocular syndrome (SANS). The etiology of SANS is unknown, but mimicking gravitational loading through AG may mitigate these negative adaptations. Seventeen subjects (9M, 8F, 18-32 years) were analyzed in four experimental conditions: 1) Standing, 2) Supine, 3) AG with the center of rotation at the eye (AGEC), 4) AG with 2G's at the feet (AG2G). In both AG conditions, subjects were spun to produce 1G at their center of mass. Data included self-administered intraocular pressure (IOP, Tonopen AVIA), heart rate (HR), and mean arterial blood pressure (MAP, Omron Series 10). Data were analyzed with repeated measures ANOVAs, with Tukey-Kramer corrections for multiple pairwise comparisons. IOP was 15.7 {plus minus} 1.4 mmHg (mean{plus minus}95% confidence interval) Standing, 18.8 {plus minus} 1.3 mmHg Supine, 18.5 {plus minus} 1.7 mmHg in AGEC, and 17.5 {plus minus} 1.5 mmHg in AG2G. Postures showed a main effect (F(3,48)=11.0, p&lt;0.0005), with Standing significantly lower than Supine (p=0.0009), AGEC (p=0.002), and AG2G (0.036). Supine, AGEC, and AG2G were not statistically different. HR and MAP were lower in Supine compared to all other postures (p=0.002 to p&lt;0.0005), but there were no differences between Standing, AGEC, and AG2G. IOP in Supine and Standing was consistent with previous studies, but contrary to our hypothesis, remained elevated in both AG conditions. Cardiovascular parameters and hydrostatic gradients determine IOP, which remain unchanged compared to Standing. These results suggest additional influence on IOP from previously unconsidered factors.</p

Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum

Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes. While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic. It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients. Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients. Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience. The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19. We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19

Training augmentation using additive sensory noise in a lunar rover navigation task

BackgroundThe uncertain environments of future space missions means that astronauts will need to acquire new skills rapidly; thus, a non-invasive method to enhance learning of complex tasks is desirable. Stochastic resonance (SR) is a phenomenon where adding noise improves the throughput of a weak signal. SR has been shown to improve perception and cognitive performance in certain individuals. However, the learning of operational tasks and behavioral health effects of repeated noise exposure aimed to elicit SR are unknown.ObjectiveWe evaluated the long-term impacts and acceptability of repeated auditory white noise (AWN) and/or noisy galvanic vestibular stimulation (nGVS) on operational learning and behavioral health.MethodsSubjects (n = 24) participated in a time longitudinal experiment to access learning and behavioral health. Subjects were assigned to one of our four treatments: sham, AWN (55 dB SPL), nGVS (0.5 mA), and their combination to create a multi-modal SR (MMSR) condition. To assess the effects of additive noise on learning, these treatments were administered continuously during a lunar rover simulation in virtual reality. To assess behavioral health, subjects completed daily, subjective questionnaires related to their mood, sleep, stress, and their perceived acceptance of noise stimulation.ResultsWe found that subjects learned the lunar rover task over time, as shown by significantly lower power required for the rover to complete traverses (p &lt; 0.005) and increased object identification accuracy in the environment (p = 0.05), but this was not influenced by additive SR noise (p = 0.58). We found no influence of noise on mood or stress following stimulation (p &gt; 0.09). We found marginally significant longitudinal effects of noise on behavioral health (p = 0.06) as measured by strain and sleep. We found slight differences in stimulation acceptability between treatment groups, and notably nGVS was found to be more distracting than sham (p = 0.006).ConclusionOur results suggest that repeatedly administering sensory noise does not improve long-term operational learning performance or affect behavioral health. We also find that repetitive noise administration is acceptable in this context. While additive noise does not improve performance in this paradigm, if it were used for other contexts, it appears acceptable without negative longitudinal effects

Training augmentation using additive sensory noise in a lunar rover navigation task

Background The uncertain environments of future space missions means that astronauts will need to acquire new skills rapidly; thus, a non-invasive method to enhance learning of complex tasks is desirable. Stochastic resonance (SR) is a phenomenon where adding noise improves the throughput of a weak signal. SR has been shown to improve perception and cognitive performance in certain individuals. However, the learning of operational tasks and behavioral health effects of repeated noise exposure aimed to elicit SR are unknown. Objective We evaluated the long-term impacts and acceptability of repeated auditory white noise (AWN) and/or noisy galvanic vestibular stimulation (nGVS) on operational learning and behavioral health.MethodsSubjects (n = 24) participated in a time longitudinal experiment to access learning and behavioral health. Subjects were assigned to one of our four treatments: sham, AWN (55 dB SPL), nGVS (0.5 mA), and their combination to create a multi-modal SR (MMSR) condition. To assess the effects of additive noise on learning, these treatments were administered continuously during a lunar rover simulation in virtual reality. To assess behavioral health, subjects completed daily, subjective questionnaires related to their mood, sleep, stress, and their perceived acceptance of noise stimulation. Results We found that subjects learned the lunar rover task over time, as shown by significantly lower power required for the rover to complete traverses (p 0.09). We found marginally significant longitudinal effects of noise on behavioral health (p = 0.06) as measured by strain and sleep. We found slight differences in stimulation acceptability between treatment groups, and notably nGVS was found to be more distracting than sham (p = 0.006). Conclusion Our results suggest that repeatedly administering sensory noise does not improve long-term operational learning performance or affect behavioral health. We also find that repetitive noise administration is acceptable in this context. While additive noise does not improve performance in this paradigm, if it were used for other contexts, it appears acceptable without negative longitudinal effects

A necroptosis-independent function of RIPK3 promotes immune dysfunction and prevents control of chronic LCMV infection

Necroptosis is a lytic and inflammatory form of cell death that is highly constrained to mitigate detrimental collateral tissue damageand impaired immunity. These constraints make it difficult to define the relevance of necroptosis in diseases such as chronic andpersistent viral infections and within individual organ systems. The role of necroptotic signalling is further complicated becauseproteins essential to this pathway, such as receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like(MLKL), have been implicated in roles outside of necroptotic signalling. We sought to address this issue by individually defining therole of RIPK3 and MLKL in chronic lymphocytic choriomeningitis virus (LCMV) infection. We investigated if necroptosis contributesto the death of LCMV-specific CD8+ T cells or virally infected target cells during infection. We provide evidence showing thatnecroptosis was redundant in the pathogenesis of acute forms of LCMV (Armstrong strain) and the early stages of chronic (Docilestrain) LCMV infection in vivo. The number of immune cells, their specificity and reactivity towards viral antigens and viral loads arenot altered in the absence of either MLKL or RIPK3 during acute and during the early stages of chronic LCMV infection. However, weidentified that RIPK3 promotes immune dysfunction and prevents control of infection at later stages of chronic LCMV disease. Thiswas not phenocopied by the loss of MLKL indicating that the phenotype was driven by a necroptosis-independent function ofRIPK3. We provide evidence that RIPK3 signaling evoked a dysregulated type 1 interferone response which we linked to animpaired antiviral immune response and abrogated clearance of chronic LCMV infectio

Ultrafast Structural Dynamics of BlsA, a Photoreceptor from the Pathogenic Bacterium Acinetobacter baumannii

Acinetobacter baumannii is an important human pathogen that can form biofilms and persist under harsh environmental conditions. Biofilm formation and virulence are modulated by blue light, which is thought to be regulated by a BLUF protein, BlsA. To understand the molecular mechanism of light sensing, we have used steady-state and ultrafast vibrational spectroscopy to compare the photoactivation mechanism of BlsA to the BLUF photosensor AppA from Rhodobacter sphaeroides. Although similar photocycles are observed, vibrational data together with homology modeling identify significant differences in the β5 strand in BlsA caused by photoactivation, which are proposed to be directly linked to downstream signaling

Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site

We introduce a novel method to screen the promoters of a set of genes with shared biological function, against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. The gene sets were obtained from the functional Gene Ontology (GO) classification; for each set and motif we optimized the sequence similarity score threshold, independently for every location window (measured with respect to the TSS), taking into account the location dependent nucleotide heterogeneity along the promoters of the target genes. We performed a high throughput analysis, searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology classes and for 412 known DNA motifs. When combined with binding site and location conservation between human and mouse, the method identifies with high probability functional binding sites that regulate groups of biologically related genes. We found many location-sensitive functional binding events and showed that they clustered close to the TSS. Our method and findings were put to several experimental tests. By allowing a "flexible" threshold and combining our functional class and location specific search method with conservation between human and mouse, we are able to identify reliably functional TF binding sites. This is an essential step towards constructing regulatory networks and elucidating the design principles that govern transcriptional regulation of expression. The promoter region proximal to the TSS appears to be of central importance for regulation of transcription in human and mouse, just as it is in bacteria and yeast.Comment: 31 pages, including Supplementary Information and figure