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Background: A vaccine against SARS-CoV-2 is of high urgency. Here the safety and immunogenicity induced by a DNA vaccine (INO-4800) targeting the full length spike antigen of SARS-CoV-2 are described. Methods: INO-4800 was evaluated in two groups of 20 participants, receiving either 1.0 mg or 2.0 mg of vaccine intradermally followed by CELLECTRA® EP at 0 and 4 weeks. Thirty-nine subjects completed both doses; one subject in the 2.0 mg group discontinued trial participation prior to receiving the second dose. ClinicalTrials.gov identifier: NCT04336410. Findings: The median age was 34.5, 55% (22/40) were men and 82.5% (33/40) white. Through week 8, only 6 related Grade 1 adverse events in 5 subjects were observed. None of these increased in frequency with the second administration. No serious adverse events were reported. All 38 subjects evaluable for immunogenicity had cellular and/or humoral immune responses following the second dose of INO-4800. By week 6, 95% (36/38) of the participants seroconverted based on their responses by generating binding (ELISA) and/or neutralizing antibodies (PRNT IC50), with responder geometric mean binding antibody titers of 655.5 [95% CI (255.6, 1681.0)] and 994.2 [95% CI (395.3, 2500.3)] in the 1.0 mg and 2.0 mg groups, respectively. For neutralizing antibody, 78% (14/18) and 84% (16/19) generated a response with corresponding geometric mean titers of 102.3 [95% CI (37.4, 280.3)] and 63.5 [95% CI (39.6, 101.8)], in the respective groups. By week 8, 74% (14/19) and 100% (19/19) of subjects generated T cell responses by IFN-ɣ ELISpot assay with the median SFU per 106 PBMC of 46 [95% CI (21.1, 142.2)] and 71 [95% CI (32.2, 194.4)] in the 1.0 mg and 2.0 mg groups, respectively. Flow cytometry demonstrated a T cell response, dominated by CD8+ T cells co-producing IFN-ɣ and TNF-α, without increase in IL-4. Interpretation: INO-4800 demonstrated excellent safety and tolerability and was immunogenic in 100% (38/38) of the vaccinated subjects by eliciting either or both humoral or cellular immune responses. Funding: Coalition for Epidemic Preparedness Innovations (CEPI).

EXPAREL® has been used successfully to prolong postoperative pain control when applied as a wound infiltrate. EXPAREL® has not yet been approved for use in regional anesthesia to prolong postoperative pain control. We conducted a clinical case series of 4 patients using EXPAREL® for sciatic blocks via the popliteal fossa approach. Our results suggested that there is a large degree of variability in response to the medication. These inconsistent results and the possibility of bimodal kinetics creating analgesic gaps as seen in two of our patients indicate that more studies with larger sample size are needed to better characterize these phenomena and determine if more consistent results can be obtained in a future clinical trial.

Ao refletir sobre a experiência através de espelhos, esse texto pensa a relação entre sujeito e imagem a partir dos conceitos de utopia e de heterotopia. Ao longo dos parágrafos, ele parte de exemplos cotidianos para se confrontar com os casos em que os direitos da imagem encontram situações limite, nomeadamente a partir de algumas reflexões de Michel Focault. Levantam-se aqui ao menos duas hipóteses importantes: a de que uma imagem utópica da existência traz perigos que não se podem menosprezar, e uma segunda sobre a possibilidade de uma alternativa capaz de rearranjar esses riscos em torno da experiência estética. Pretende-se com isso fomentar o debate ligado à discussão sobre nossa capacidade de dar conta das imagens que transmitimos para nós mesmos.

The United States (US) aviation industry provides a potentially useful mental model for dealing with certain cost-benefit decisions in aesthesiology. The Federal Aviation Administration (FAA), the national aviation authority of the United States, quantifies a price for the value of a human life based on the U.S. Department of Transportation’s (DOT) value of a statistical life (VSL) unit. The current VSL is around $9.6 million, indexed to grow with consideration given to inflation and wage changes from the 2016 baseline of $9.4 million [1]. To illustrate the concept, if the FAA estimates that 100 people are likely to die in the future given the current practice standards then the monetary cost of this loss will be $940 million. The FAA uses this estimated monetary value as an official reference point in its regulatory decisions, and the agency publishes in detail how it derives the estimated value. When proposing new regulations, the FAA bases its decisions on comparisons of the human life cost associated with the existing regulation versus the alternative cost that the industry stakeholders will incur subsequent to the adoption of the regulation. In this example, if the cost incurred by the industry is more than the $940 million cost then the FAA will not adopt the proposed regulation and hence will not require the industry to undertake this cost.

Background Because COVID-19 case data do not capture most SARS-CoV-2 infections, the actual risk of severe disease and death per infection is unknown. Integrating sociodemographic data into analysis can show consequential health disparities. Methods Data were merged from September 2020 to November 2021 from 6 national surveillance systems in matched geographic areas and analyzed to estimate numbers of COVID-19–associated cases, emergency department visits, and deaths per 100 000 infections. Relative risks of outcomes per infection were compared by sociodemographic factors in a data set including 1490 counties from 50 states and the District of Columbia, covering 71% of the US population. Results Per infection with SARS-CoV-2, COVID-19–related morbidity and mortality were higher among non-Hispanic American Indian and Alaska Native persons, non-Hispanic Black persons, and Hispanic or Latino persons vs non-Hispanic White persons; males vs females; older people vs younger; residents in more socially vulnerable counties vs less; those in large central metro areas vs rural; and people in the South vs the Northeast. Discussion Meaningful disparities in COVID-19 morbidity and mortality per infection were associated with sociodemography and geography. Addressing these disparities could have helped prevent the loss of tens of thousands of lives. [ABSTRACT FROM AUTHOR]

This action research was made to utilize the TRIO GC for tracking the students' performance in Mathematics 8. This was conducted on 120 students from selected Grade 8 students with difficulties in performing well in class. To assess students' mathematical performance, the researchers got the mean grade of the first semester and correlated it to the second semester after giving intervention. The researchers used a mixed-method research design. Both parents and students answered the questionnaires using the Likert scale. An interview was also conducted with the students for triangulation. The result showed that the respondents demonstrated significant growth in their mathematical performance after using the TRIO GC from a mean of 81% in the first semester to 85% in the second semester. This was proven by getting the significance using t-test correlation-dependent samples where the computed T value of 10.244 was greater than the tabular T value of 1.98 two-tailed at 0.05 level of significance. The computed value is outside the acceptance area so the null hypothesis is rejected, which means that there is a significant difference after the treatment. Thus, the result was further supported by the follow-up interview to the students about the survey questionnaire wherein they cited commendable remarks on their experiences while using TRIO GC. [ABSTRACT FROM AUTHOR]

Background: As the largest organ in the human body, the skin is continuously exposed to intrinsic and extrinsic stimuli that impact its functionality and morphology with aging. Skin aging entails dysregulation of skin cells and loss, fragmentation, or fragility of extracellular matrix fibers that are manifested macroscopically by wrinkling, laxity, and pigmentary abnormalities. Age-related skin changes are the focus of many surgical and nonsurgical treatments aimed at improving overall skin appearance and health. Summary: As a hallmark of aging, cellular senescence, an essentially irreversible cell cycle arrest with apoptosis resistance and a secretory phenotype, manifests across skin layers by affecting epidermal and dermal cells. Knowledge of skin-specific senescent cells, such as melanocytes (epidermal aging) and fibroblasts (dermal aging), will promote our understanding of age-related skin changes and how to optimize patient outcomes in esthetic procedures. Key Messages: This review provides an overview of skin aging in the context of cellular senescence and discusses senolytic intervention strategies to selectively target skin senescent cells that contribute to premature skin aging. [ABSTRACT FROM AUTHOR]

Resprouting is a plant persistence strategy in response to disturbance or stressful environmental conditions. Resprouters can dominate in stressful environments such as tropical dry forests (TDFs), but our knowledge of resprouting in TDFs is limited. Here, using a dataset of forest inventories in 16 TDF fragments (covering 15,642 trees and 321 species), we investigated patterns of resprouting in ecosystems subject to substantial seasonal water stress. We focused on two resprouting metrics: the proportion of trees that are multistemmed (resprouting frequency) and the number of stems per tree. In addition, we investigated the relative importance of environmental factors, taxonomic identity, and evolutionary history in resprouting response. Taxa with low to medium resprouting frequencies (17.19%–40.2%) are the most prevalent in TDF, compared to non‐resprouters and high‐frequency resprouters. Overall, resprouting ability appears to be an intrinsic trait that varies in response to environmental conditions but only within a range constrained by taxonomic identity. However, we found no phylogenetic signal above the genus level for any resprouting variables. Thus, the variation in resprouting across TDF lineages likely has been shaped by divergence between closely related taxa and convergence between distantly related ones, reflecting the specific environmental and disturbance factors to which they have been subjected. [ABSTRACT FROM AUTHOR]

Despite the perception that treatment of glabellar lines with botulinum toxin A (BoNTA) is straightforward, the reality is that the glabellar region contains a number of interrelated muscles. In order to avoid adverse outcomes, practitioners need to appreciate how treatment of one facial muscle group influences the relative dominance of others. In particular, practitioners need to understand the independent role of the frontalis in eyebrow outcomes and the potential for negative outcomes if the lower frontalis is unintentionally weakened by BoNTA treatment. In addition, practitioners must recognize how inter-individual variation in the depth, shape, and muscle fiber orientation among the upper facial muscles can affect outcomes. For optimal results, treatment of the glabellar complex requires a systematic and individualized approach that is based on anatomical principles of opposing muscle actions rather than a one-size-fits-all approach. This review provides the anatomical justification for the importance of an integrated assessment of the upper facial muscles and eyebrow position prior to glabellar treatment. In addition, a systematic and broad evaluation system is provided that can be used by practitioners to more comprehensively assess the glabellar region in order to optimize outcomes and avoid negatively impacting resting brow position and dynamic brow movement. [ABSTRACT FROM AUTHOR]

This research investigated the self-reported mainstream school experiences of those diagnosed on the autistic spectrum compared with the typically developing school population. Existing literature identifies four key areas that affect the quality of the school experience for students with autism: social skills, perceived relationships with teaching staff, general school functioning, and interpersonal strengths of the young person. These areas were explored in a mainstream U.K. secondary school with 14 students with autism and 14 age and gender matched students without autism, using self-report questionnaires and semi-structured interviews. Quantitative analyses showed consistent school experiences for both groups, although content analysis of interview data highlighted some differences in the ways in which the groups perceive group work, peers, and teaching staff within school. Implications for school inclusion are discussed, drawing attention to how staff awareness of autism could improve school experience and success for students with autism attending mainstream schools.