Traversable wormhole dynamics on a quantum processor.

The holographic principle, theorized to be a property of quantum gravity, postulates that the description of a volume of space can be encoded on a lower-dimensional boundary. The anti-de Sitter (AdS)/conformal field theory correspondence or duality1 is the principal example of holography. The Sachdev-Ye-Kitaev (SYK) model of N ≫ 1 Majorana fermions2,3 has features suggesting the existence of a gravitational dual in AdS2, and is a new realization of holography4-6. We invoke the holographic correspondence of the SYK many-body system and gravity to probe the conjectured ER=EPR relation between entanglement and spacetime geometry7,8 through the traversable wormhole mechanism as implemented in the SYK model9,10. A qubit can be used to probe the SYK traversable wormhole dynamics through the corresponding teleportation protocol9. This can be realized as a quantum circuit, equivalent to the gravitational picture in the semiclassical limit of an infinite number of qubits9. Here we use learning techniques to construct a sparsified SYK model that we experimentally realize with 164 two-qubit gates on a nine-qubit circuit and observe the corresponding traversable wormhole dynamics. Despite its approximate nature, the sparsified SYK model preserves key properties of the traversable wormhole physics: perfect size winding11-13, coupling on either side of the wormhole that is consistent with a negative energy shockwave14, a Shapiro time delay15, causal time-order of signals emerging from the wormhole, and scrambling and thermalization dynamics16,17. Our experiment was run on the Google Sycamore processor. By interrogating a two-dimensional gravity dual system, our work represents a step towards a program for studying quantum gravity in the laboratory. Future developments will require improved hardware scalability and performance as well as theoretical developments including higher-dimensional quantum gravity duals18 and other SYK-like models19.

Mucosal antibody responses following Vaxzevria vaccination.

Mucosal antibodies play a key role in protection against breakthrough COVID-19 infections and emerging viral variants. Intramuscular adenovirus-based vaccination (Vaxzevria) only weakly induces nasal IgG and IgA responses, unless vaccinees have been previously infected. However, little is known about how Vaxzevria vaccination impacts the ability of mucosal antibodies to induce Fc responses, particularly against SARS-CoV-2 variants of concern (VoCs). Here, we profiled paired mucosal (saliva, tears) and plasma antibodies from COVID-19 vaccinated only vaccinees (uninfected, vaccinated) and COVID-19 recovered vaccinees (COVID-19 recovered, vaccinated) who both received Vaxzevria vaccines. SARS-CoV-2 ancestral-specific IgG antibodies capable of engaging FcγR3a were significantly higher in the mucosal samples of COVID-19 recovered Vaxzevria vaccinees in comparison with vaccinated only vaccinees. However, when IgG and FcγR3a engaging antibodies were tested against a panel of SARS-CoV-2 VoCs, the responses were ancestral-centric with weaker recognition of Omicron strains observed. In contrast, salivary IgA, but not plasma IgA, from Vaxzevria vaccinees displayed broad cross-reactivity across all SARS-CoV-2 VoCs tested. Our data highlight that while intramuscular Vaxzevria vaccination can enhance mucosal antibodies responses in COVID-19 recovered vaccinees, restrictions by ancestral-centric bias may have implications for COVID-19 protection. However, highly cross-reactive mucosal IgA could be key in addressing these gaps in mucosal immunity and may be an important focus of future SARS-CoV-2 vaccine development.

Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants.

Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge to worldwide public health. The SARS-CoV-2 receptor-binding domain (RBD) is a hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated the impact of RBD mutations, including 5 variants of concern (VOC) or interest-including Omicron (BA.2)-and 33 common point mutations, both on IgG recognition and ACE2-binding inhibition, as well as FcγRIIa- and FcγRIIIa-binding antibodies, in plasma from two-dose BNT162b2-vaccine recipients and mild-COVID-19 convalescent subjects obtained during the first wave using a custom-designed bead-based 39-plex array. IgG-recognition and FcγR-binding antibodies were decreased against the RBD of Beta and Omicron, as well as point mutation G446S, found in several Omicron sub-variants as compared to wild type. Notably, while there was a profound decrease in ACE2 inhibition against Omicron, FcγR-binding antibodies were less affected, suggesting that Fc functional antibody responses may be better retained against the RBD of Omicron in comparison to neutralization. Furthermore, while measurement of RBD-ACE2-binding affinity via biolayer interferometry showed that all VOC RBDs have enhanced affinity to human ACE2, we demonstrate that human ACE2 polymorphisms, E35K (rs1348114695) has reduced affinity to VOCs, while K26R (rs4646116) and S19P (rs73635825) have increased binding kinetics to the RBD of VOCs, potentially affecting virus-host interaction and, thereby, host susceptibility. Collectively, our findings provide in-depth coverage of the impact of RBD mutations on key facets of host-virus interactions.

Covid-19, social restrictions, and mental distress among young people: a UK longitudinal, population-based study.

BACKGROUND: Adolescence is a critical period for social and emotional development. We sought to examine the impacts of Covid-19 and related social restrictions and school closures on adolescent mental health, particularly among disadvantaged, marginalised, and vulnerable groups. METHODS: We analysed four waves of data - 3 pre-Covid-19 (2016-2019) and 1 mid-Covid-19 (May-Aug 2020; n, 1074; 12-18 years old, >80% minority ethnic groups, 25% free school meals) from REACH (Resilience, Ethnicity, and AdolesCent Mental Health), an adolescent cohort based in inner-London, United Kingdom. Mental health was assessed using validated measures at each time point. We estimated temporal trends in mental distress and examined variations in changes in distress, pre- to mid-Covid-19, by social group, and by pre- and mid-pandemic risks. RESULTS: We found no evidence of an overall increase in mental distress midpandemic (15.9%, 95% CI: 13.0, 19.4) compared with prepandemic (around 18%). However, there were variations in changes in mental distress by subgroups. There were modest variations by social group and by pre-Covid risks (e.g., a small increase in distress among girls (b [unstandardised beta coefficient] 0.42 [-0.19, 1.03]); a small decrease among boys (b - 0.59 [-1.37, 0.19]); p for interaction .007). The most notable variations were by midpandemic risks: that is, broadly, increases in distress among those reporting negative circumstances and impacts (e.g., in finances, housing, social support and relationships, and daily routines) and decreases in distress among those reporting positive impacts. CONCLUSIONS: We found strong evidence that mental distress increased among young people who were most negatively impacted by Covid-19 and by related social restrictions during the first lockdown in the United Kingdom.

AAV9 Gene Therapy Increases Lifespan and Treats Pathological and Behavioral Abnormalities in a Mouse Model of CLN8-Batten Disease.

CLN8 disease is a rare form of neuronal ceroid lipofuscinosis caused by biallelic mutations in the CLN8 gene, which encodes a transmembrane endoplasmic reticulum protein involved in trafficking of lysosomal enzymes. CLN8 disease patients present with myoclonus, tonic-clonic seizures, and progressive declines in cognitive and motor function, with many cases resulting in premature death early in life. There are currently no treatments that can cure the disease or substantially slow disease progression. Using a mouse model of CLN8 disease, we tested the safety and efficacy of an intracerebroventricularly (i.c.v.) delivered self-complementary adeno-associated virus serotype 9 (scAAV9) gene therapy vector driving expression of human CLN8. A single neonatal injection was safe and well tolerated, resulting in robust transgene expression throughout the CNS from 4 to 24 months, reducing histopathological and behavioral hallmarks of the disease and restoring lifespan from 10 months in untreated animals to beyond 24 months of age in treated animals. While it is unclear whether some of these behavioral improvements relate to preserved visual function, improvements in learning/memory, or other central or peripheral benefits, these results demonstrate, by far, the most successful degree of rescue reported in an animal model of CLN8 disease, and they support further development of gene therapy for this disorder.

Exploring factors affecting individual GPS-based activity space and how researcher-defined food environments represent activity space, exposure and use of food outlets.

BACKGROUND: Obesity remains one of the most challenging public health issues of our modern time. Despite the face validity of claims for influence, studies on the causes of obesity have reported the influence of the food environment to be inconsistent. This inconsistency has been attributed to the variability of measures used by researchers to represent the food environments-Researcher-Defined Food Environments (RDFE) like circular, street-network buffers, and others. This study (i.) determined an individual's Activity Space (AS) (ii.) explored the accuracy of the RDFE in representing the AS, (iii.) investigated the accuracy of the RDFE in representing actual exposure, and (iv.) explored whether exposure to food outlet reflects the use of food outlets. METHODS: Data were collected between June and December 2018. A total of 65 participants collected Global Positioning System (GPS) data, kept receipt of all their food purchases, completed a questionnaire about their personal information and had their weight and height measured. A buffer was created around the GPS points and merged to form an AS (GPS-based AS). RESULTS: Statistical and geospatial analyses found that the AS size of participants working away from home was positively related to the Euclidean distance from home to workplace; the orientation (shape) of AS was also influenced by the direction of workplace from home and individual characteristics were not predictive of the size of AS. Consistent with some previous studies, all types and sizes of RDFE variably misrepresented individual exposure in the food environments. Importantly, the accuracy of the RDFE was significantly improved by including both the home and workplace domains. The study also found no correlation between exposure and use of food outlets. CONCLUSIONS: Home and workplace are key activity nodes in modelling AS or food environments and the relationship between exposure and use is more complex than is currently suggested in both empirical and policy literature.

Serum IgA Fc effector functions in infectious disease and cancer.

Immunoglobulin (Ig) A is the most abundant antibody isotype present at mucosal surfaces and the second most abundant in human serum. In addition to preventing pathogen entry at mucosal surfaces, IgA can control and eradicate bacterial and viral infections through a variety of antibody-mediated innate effector cell mechanisms. The role of mucosal IgA in infection (e.g. neutralization) and in inflammatory homeostasis (e.g. allergy and autoimmunity) has been extensively investigated; by contrast, serum IgA is comparatively understudied. IgA binding to fragment crystallizable alpha receptor plays a dual role in the activation and inhibition of innate effector cell functions. Mounting evidence suggests that serum IgA induces potent effector functions against various bacterial and some viral infections including Neisseria meningitidis and rotavirus. Furthermore, in the era of immunotherapy, serum IgA provides an interesting alternative to classical IgG monoclonal antibodies to treat cancer and infectious pathogens. Here we discuss the role of serum IgA in infectious diseases with reference to bacterial and viral infections and the potential for IgA as a monoclonal antibody therapy.

Gene Therapy Corrects Brain and Behavioral Pathologies in CLN6-Batten Disease.

CLN6-Batten disease, a form of neuronal ceroid lipofuscinosis is a rare lysosomal storage disorder presenting with gradual declines in motor, visual, and cognitive abilities and early death by 12-15 years of age. We developed a self-complementary adeno-associated virus serotype 9 (scAAV9) vector expressing the human CLN6 gene under the control of a chicken ß-actin (CB) hybrid promoter. Intrathecal delivery of scAAV9.CB.hCLN6 into the cerebrospinal fluid (CSF) of the lumbar spinal cord of 4-year-old non-human primates was safe, well tolerated, and led to efficient targeting throughout the brain and spinal cord. A single intracerebroventricular (i.c.v.) injection at post-natal day 1 in Cln6 mutant mice delivered scAAV9.CB.CLN6 directly into the CSF, and it prevented or drastically reduced all of the pathological hallmarks of Batten disease. Moreover, there were significant improvements in motor performance, learning and memory deficits, and survival in treated Cln6 mutant mice, extending survival from 15 months of age (untreated) to beyond 21 months of age (treated). Additionally, many parameters were similar to wild-type counterparts throughout the lifespan of the treated mice.

Correction: Documenting Social Media Engagement as Scholarship: A New Model for Assessing Academic Accomplishment for the Health Professions.

[This corrects the article DOI: 10.2196/25070.].

Documenting Social Media Engagement as Scholarship: A New Model for Assessing Academic Accomplishment for the Health Professions.

BACKGROUND: The traditional model of promotion and tenure in the health professions relies heavily on formal scholarship through teaching, research, and service. Institutions consider how much weight to give activities in each of these areas and determine a threshold for advancement. With the emergence of social media, scholars can engage wider audiences in creative ways and have a broader impact. Conventional metrics like the h-index do not account for social media impact. Social media engagement is poorly represented in most curricula vitae (CV) and therefore is undervalued in promotion and tenure reviews. OBJECTIVE: The objective was to develop crowdsourced guidelines for documenting social media scholarship. These guidelines aimed to provide a structure for documenting a scholar's general impact on social media, as well as methods of documenting individual social media contributions exemplifying innovation, education, mentorship, advocacy, and dissemination. METHODS: To create unifying guidelines, we created a crowdsourced process that capitalized on the strengths of social media and generated a case example of successful use of the medium for academic collaboration. The primary author created a draft of the guidelines and then sought input from users on Twitter via a publicly accessible Google Document. There was no limitation on who could provide input and the work was done in a democratic, collaborative fashion. Contributors edited the draft over a period of 1 week (September 12-18, 2020). The primary and secondary authors then revised the draft to make it more concise. The guidelines and manuscript were then distributed to the contributors for edits and adopted by the group. All contributors were given the opportunity to serve as coauthors on the publication and were told upfront that authorship would depend on whether they were able to document the ways in which they met the 4 International Committee of Medical Journal Editors authorship criteria. RESULTS: We developed 2 sets of guidelines: Guidelines for Listing All Social Media Scholarship Under Public Scholarship (in Research/Scholarship Section of CV) and Guidelines for Listing Social Media Scholarship Under Research, Teaching, and Service Sections of CV. Institutions can choose which set fits their existing CV format. CONCLUSIONS: With more uniformity, scholars can better represent the full scope and impact of their work. These guidelines are not intended to dictate how individual institutions should weigh social media contributions within promotion and tenure cases. Instead, by providing an initial set of guidelines, we hope to provide scholars and their institutions with a common format and language to document social media scholarship.

Psychometric properties and correlates of a brief scale measuring the psychological construct mattering to others in a sample of women recovering from breast cancer.

PURPOSE: Mattering to others, or perceiving one is a significant part of the social world, may be important to breast cancer survivors' quality of life. This study examines the reliability and validity of the 5-item general mattering scale (GMS) to assess mattering in breast cancer survivors. METHODS: A secondary analysis and confirmatory factor analysis (CFA) were performed on data from an intervention study with breast cancer survivors that included the GMS and other psychological measures. RESULTS: The unidimensional representation of the GMS was consistent with the data (χ2 = 8.102; df = 4; p = .088). The scale was highly reliable as indicated by McDonald's omega of .84. The scale was significantly correlated with all psychological measures in the predicted direction except anxiety. After controlling for social support, the scale was significantly, positively correlated with functional quality of life, self-esteem, positive affect, and having meaning in life. Mattering was significantly, negatively correlated with searching for meaning. Significantly higher level of mattering was found among married participants and among women who had not obtained psychological therapy. CONCLUSIONS: The 5-item GMS is a practical, reliable, and valid tool the measuring mattering to others among breast cancer survivors.

Partial compensation to delayed auditory feedback: An analysis of syllable duration.

Altered feedback perturbation studies have shown that speakers only partially compensate for shifts in vocal pitch, intensity, or spectral content. The partial compensation generally plateaus around 30%-40% of the non-shifted, baseline production and is proposed to reflect the integrated effect of altered (auditory) and non-altered (somatosensory) sensory feedback. The authors hypothesized that the same pattern should hold for changes in syllable duration with delayed auditory feedback. To test this, the authors calculated average syllable duration from 21 young adults who read a standard passage as auditory feedback was delayed by 0, 10, 50, 100, 200, 300, and 600 ms. Given the complex nature of speech errors elicited under delayed auditory feedback, the authors compared durational effects across two broad error categories: prolongations and repetitions. Average syllable duration increased non-linearly and reached a peak near 40% of baseline durations. Separated by error type, prolongations, and distortions made up 89% of perceived errors. Only 9% of perceived errors were identified as repetitions. Unlike prolongations, however, the duration of repeated tokens ranged from 74% to 110% of the target syllable and compensated fully for the delay. These results are consistent with the notion that increasing syllable duration compensates partially for delays in auditory feedback. The compensation pattern resembles that of responses to other forms of altered auditory feedback, which suggests that this may be a general attribute of low-level, sensorimotor compensation. The higher frequency of prolongation occurrences further suggests that these may be the primary means of compensation for delayed auditory feedback. Repetitions, on the other hand, likely reflect compensatory mechanisms of higher-level motor planning or sequencing processes.

Influence of Resonances on the Noise Performance of SQUID Susceptometers.

Scanning Superconducting Quantum Interference Device (SQUID) Susceptometry simultaneously images the local magnetic fields and susceptibilities above a sample with sub-micron spatial resolution. Further development of this technique requires a thorough understanding of the current, voltage, and flux ( I V Φ ) characteristics of scanning SQUID susceptometers. These sensors often have striking anomalies in their current-voltage characteristics, which we believe to be due to electromagnetic resonances. The effect of these resonances on the performance of these SQUIDs is unknown. To explore the origin and impact of the resonances, we develop a model that qualitatively reproduces the experimentally-determined I V Φ characteristics of our scanning SQUID susceptometers. We use this model to calculate the noise characteristics of SQUIDs of different designs. We find that the calculated ultimate flux noise is better in susceptometers with damping resistors that diminish the resonances than in susceptometers without damping resistors. Such calculations will enable the optimization of the signal-to-noise characteristics of scanning SQUID susceptometers.

The Risk of Necrotizing Enterocolitis Differs Among Preterm Pigs Fed Formulas With Either Lactose or Maltodextrin.

OBJECTIVES: When breast milk is unavailable for preterm infants, formulas are needed that won't increase the risk of necrotizing enterocolitis (NEC). Adding novel ingredients to formula to reduce NEC has not been effective clinically. Instead, we tested the prediction that NEC can be reduced by removing the maltodextrin now included in preterm formulas. METHODS: The preterm pig model of spontaneous NEC was used to evaluate growth, health, and intestinal responses to 6 to 7 days of feeding formulas that were identical except for the source of carbohydrate; either 100% lactose or maltodextrin; colostrum was used as the control. RESULTS: Formula with maltodextrin resulted in a 50% incidence of NEC with 30% mortality. The lactose formula and colostrum resulted in a 0% incidence of NEC. Growth was highest for pigs fed the formula with lactose, intermediate with maltodextrin, and minimal when bovine colostrum was fed (P < 0.05). Although the small intestine was larger when colostrum was fed (P < 0.05), because rates of glucose uptake were lower (P < 0.05), total small intestine capacities to transport glucose were similar for healthy pigs in all 3 groups. CONCLUSIONS: If lactose-based formulas reduce NEC clinically, the transition of preterm infants to enteral feeding can be accelerated, improving growth and development, and shortening reliance on parenteral nutrition. Although colostrum protects against NEC, chronic feeding does not promote body weight gain after preterm birth. The preterm pig can be used for preclinical studies that evaluate the mechanisms by which carbohydrates and other ingredients influence growth, development, health, and risk of NEC.

How Does Garlic Mustard Lure and Kill the West Virginia White Butterfly?

As it pertains to insect herbivores, the preference-performance hypothesis posits that females will choose oviposition sites that maximize their offspring's fitness. However, both genetic and environmental cues contribute to oviposition preference, and occasionally "oviposition mistakes" occur, where insects oviposit on hosts unsuitable for larval development. Pieris virginiensis is a pierine butterfly native to North America that regularly oviposits on an invasive plant, Alliaria petiolata, but the caterpillars are unable to survive. Alliaria petiolata has high concentrations of the glucosinolate sinigrin in its tissues, as well as a hydroxynitrile glucoside, alliarinoside. We investigated sinigrin as a possible cause of mistake oviposition, and sinigrin and alliarinoside as possible causes of larval mortality. We found that sinigrin applied to leaves of Cardamine diphylla, a major host of P. virginiensis that does not produce sinigrin, had no effect on oviposition rates. We tested the effect of sinigrin on larval performance using two host plants, one lacking sinigrin (C. diphylla) and one with sinigrin naturally present (Brassica juncea). We found no effect of sinigrin application on survival of caterpillars fed C. diphylla, but sinigrin delayed pupation and decreased pupal weight. On B. juncea, sinigrin decreased survival, consumption, and caterpillar growth. We also tested the response of P. virginiensis caterpillars to alliarinoside, a compound unique to A. petiolata, which was applied to B. oleracea. We found a significant reduction in survival, leaf consumption, and caterpillar size when alliarinoside was consumed. The 'novel weapon' alliarinoside likely is largely responsible for larval failure on the novel host A. petiolata. Sinigrin most likely contributes to the larval mortality observed, however, we did not observe any effect of sinigrin on oviposition by P. virginiensis females. Further research needs to be done on non-glucosinolate contact cues, and volatile signals that may induce P. virginiensis oviposition.

Glucosinolate-related glucosides in Alliaria petiolata: sources of variation in the plant and different metabolism in an adapted specialist herbivore, Pieris rapae.

Specialized metabolites in plants influence their interactions with other species, including herbivorous insects, which may adapt to tolerate defensive phytochemicals. The chemical arsenal of Alliaria petiolata (garlic mustard, Brassicaceae) includes the glucosinolate sinigrin and alliarinoside, a hydroxynitrile glucoside with defensive properties to glucosinolate-adapted specialists. To further our understanding of the chemical ecology of A. petiolata, which is spreading invasively in North America, we investigated the metabolite profile and here report a novel natural product, petiolatamide, which is structurally related to sinigrin. In an extensive study of North American populations of A. petiolata, we demonstrate that genetic population differences as well as developmental regulation contribute to variation in the leaf content of petiolatamide, alliarinoside, sinigrin, and a related glycoside. We furthermore demonstrate widely different metabolic fates of these metabolites after ingestion in the glucosinolate-adapted herbivore Pieris rapae, ranging from simple passage over metabolic conversion to sequestration. The differences in metabolic fate were influenced by plant ß-glucosidases, insect-mediated degradation, and the specificity of the larval gut transport system mediating sequestration.

Multisensory strategies for postural compensation after lateral line loss.

To control elevation underwater, aquatic vertebrates integrate multisensory information (e.g., vestibular, visual, proprioceptive) to guide posture and swim kinematics. Here we characterized how larval zebrafish changed posture and locomotive strategies after imposed instability (decreased buoyancy) in the presence and absence of visual cues. We discovered that larvae sank more after acute loss of lateral line (flow-sensing) hair cells. In response, larvae engaged different compensatory strategies, depending on whether they were in the light or dark. In the dark, larvae swam more frequently, engaging their trunk to steer their nose up and climb more effectively. However, in the light, larvae climbed more often, engaging both pectoral fins and trunk to elevate. We conclude that larvae sense instability and use vestibular and visual information as available to control posture and trajectory. Our work is a step towards understanding the multisensory neural computations responsible for control strategies that allow orientation and navigation in depth.

Comparison of coagulation and fibrinolysis in Irish Wolfhounds and age-matched control dogs using tissue plasminogen activator-augmented viscoelastic testing.

OBJECTIVE: To determine if Irish Wolfhounds (IWs), like other sighthounds, are hyperfibrinolytic compared with nonsighthound dogs using 2 native and tissue plasminogen activator (tPA)-enhanced viscoelastic assays, one that is whole blood-based (viscoelastic coagulation monitor [VCM]) and the other that is plasma-based thromboelastography (TEG). DESIGN: Cohort study. SETTING: University teaching hospital. ANIMALS: A convenience sample of 27 IWs recruited from the Irish Wolfhound Association of New England Specialty and the local community, and 27 healthy, age-matched, large-breed control dogs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples including CBC, biochemistry, traditional coagulation, and viscoelastic testing were collected from IWs and control dogs. Twelve IWs had viscoelastic testing. IWs had lower fibrinogen concentrations (215.5 ± 57.8 vs 251.4 ± 64.5 mg/dL, P = 0.034) and formed weaker clots on both whole-blood VCM and plasma TEG assays (maximum clot firmness [VCM-MCF] = 39.4 [25.1-48.8] vs 48.5 [34.6-57.3], P = 0.0042; maximum amplitude [TEG-MA] = 22.7 [14.7-33.6] vs 32.2 [26.9-42.0], P < 0.0001). IWs were hyperfibrinolytic compared with control dogs on VCM whole-blood assays, with 25 U/mL tPA (lysis at 30 min [VCM-LI30] = 68.1 [0-100] vs\ 99.9 [63.3-100], P = 0.0009; lysis at 45 min [VCM-LI45] = 31.0 [0-100] vs 98.1 [38.4-100], P = 0.0002) but hypofibrinolytic compared with controls on TEG plasma assays with 50 U/mL tPA (lysis at 30 min [TEG-LY30] = 45.7 [4.6-94.6] vs 93.7 [12.3-96.5], P = 0.0004; lysis at 60 min [TEG-LY60] = 68.7 [29.7-96.8] vs 95.7 [34.4-97.6], P = 0.0003). Minimal fibrinolysis was measured on whole-blood VCM or plasma TEG assays without the addition of tPA, and there were no differences between the 2 groups. CONCLUSIONS: Weaker clots were found in IWs than control dogs. With the addition of tPA, IWs had evidence of hyperfibrinolysis on whole-blood VCM assays and hypofibrinolysis on plasma TEG assays compared with control dogs. Without the addition of tPA, however, both groups of dogs showed minimal fibrinolysis on viscoelastic testing.

Randomized Trial to Assess the Safety and Tolerability of Daily Intake of an Allulose Amino Acid-Based Hydration Beverage in Men and Women.

BACKGROUND: Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or humid scenarios, may be at particular risk for dehydration with ensuing loss of electrolytes, leading to sluggishness and impaired physical performance. METHODS: We evaluated an electrolyte and amino acid product containing L-alanine and L-glutamine, as well as select vitamins [B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), and vitamin C (ascorbic acid)]. Subjects (n = 40; four groups, n = 10) were randomized to consume either a placebo packet or one, two, or three packets daily of the test product for 4 weeks with site visits at 0, 2, and 4 weeks. We tested safety and tolerability by analyzing hematological parameters (complete blood counts), metabolic parameters (hepatic, renal, acid-base balance), urinalysis end products, thyroid status [T3 (triiodothyronine), T4 (thyroxine), TSH (thyroid-stimulating hormone)], tolerability (via questionnaire), vital signs, and dietary intake. RESULTS: Statistical analyses displayed ten significant main effects (p < 0.05) with white blood cells, lymphocytes, neutrophils, urinary pH, thyroxine, urination frequency, calcium, calories, fat, and cholesterol. Interactions for time and group (p < 0.05) were observed for MCV, eGFR, potassium, overall tolerability, bloating, and cramping-demonstrating mild GA disturbances. Little to no change of physiological relevance was noted for any outcome variable, regardless of dosing level. CONCLUSIONS: Our results indicate the product was well-tolerated at all dosing levels and no significant adverse changes occurred in any of the test parameters compared to the placebo group, indicating relative safety of ingestion over a 4-week treatment period, at the volumes used, and outside the context of physical stress.

Cerebral hemodynamic changes after haploidentical hematopoietic stem cell transplant in adults with sickle cell disease.

ABSTRACT: Preliminary evidence from a series of 4 adults with sickle cell disease (SCD) suggests that hematopoietic stem cell transplant (HSCT) improves cerebral hemodynamics. HSCT largely normalizes cerebral hemodynamics in children with SCD. We tested the hypothesis in adults with SCD that cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) measured using magnetic resonance imaging, normalized to healthy values, comparing measurements from ∼1 month before to 12 to 24 months after HSCT (n = 11; age, 33.3 ± 8.9 years; 389 ± 150 days after HSCT) with age-, race- and sex-matched values from healthy adults without sickle trait (n = 28; age, 30.2 ± 5.6 years). Before transplant, 7 patients had neurological indications for transplant (eg, overt stroke) and 4 had nonneurological reasons for haploidentical bone marrow transplant (haplo-BMT). All received haplo-BMT from first-degree relatives (parent, sibling, or child donor) with reduced-intensity preparation and maintained engraftment. Before transplant, CBF was elevated (CBF, 69.11 ± 24.7 mL/100 g/min) compared with that of controls (P = .004). Mean CBF declined significantly after haplo-BMT (posttransplant CBF, 48.2 ± 13.9 mL/100 g/min; P = .003). OEF was not different from that of controls at baseline and did not change significantly after haplo-BMT (pretransplant, 43.1 ± 6.7%; posttransplant, 39.6 ± 7.0%; P = .34). After transplant, CBF and OEF were not significantly different from controls (CBF, 48.2 ± 13.4 mL/100 g/min; P = .78; and OEF, 39.6 ± 7.0%; P > .99). CMRO2 did not change significantly after haplo-BMT (pretransplant, 3.18 ± 0.87 mL O2/100 g/min; posttransplant, 2.95 ± 0.83; P = .56). Major complications of haplo-BMT included 1 infection-related death and 1 severe chronic graft-versus-host disease. Haplo-BMT in adults with SCD reduces CBF to that of control values and maintains OEF and CMRO2 on average at levels observed in healthy adult controls. The trial was registered at www.clinicaltrials.gov as #NCT01850108.