Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the ...spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients-despite a decline in total S-specific antibodies-neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that-compared with mRNA vaccination-natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.
The SARS-CoV-2 pandemic has impacted public health systems all over the world. The Delta variant seems to possess enhanced transmissibility, but no clear evidence suggests it has increased virulence. ...Our data show that pre-exposed individuals had similar neutralizing activity against the authentic COVID-19 strain and the Delta and Epsilon variants. After only one vaccine dose, the neutralization capacity expanded to all tested variants in pre-exposed individuals. Healthy vaccinated individuals showed a limited breadth of neutralization. One vaccine dose did induce similar neutralizing antibodies against the Delta as against the authentic strain. However, even after two doses, this capacity only expanded to the Epsilon variant.
In melanoma, predicting which tumors will ultimately metastasize guides treatment decisions. Transcriptional signatures of primary tumors have been utilized to predict metastasis, but which among ...these are driver or passenger events remains unclear. We used data from the adjuvant AVAST-M trial to identify a predictive gene signature in localized tumors that ultimately metastasized. Using a zebrafish model of primary melanoma, we interrogated the top genes from the AVAST-M signature in vivo. This identified GRAMD1B, a cholesterol transfer protein, as a bona fide metastasis suppressor, with a majority of knockout animals rapidly developing metastasis. Mechanistically, excess free cholesterol or its metabolite 27-hydroxycholesterol promotes invasiveness via activation of an AP-1 program, which is associated with increased metastasis in humans. Our data demonstrate that the transcriptional seeds of metastasis are embedded within localized tumors, suggesting that early targeting of these programs can be used to prevent metastatic relapse.
We analyzed human melanoma transcriptomics data to identify a gene signature predictive of metastasis. To rapidly test clinical signatures, we built a genetic metastasis platform in adult zebrafish and identified GRAMD1B as a suppressor of melanoma metastasis. GRAMD1B-associated cholesterol overload activates an AP-1 program to promote melanoma invasion. This article is highlighted in the In This Issue feature, p. 1.
Malaria remains a major global public health problem with an estimated 200 million cases detected in 2012. Although the most advanced candidate malaria vaccine (RTS,S) has shown promise in clinical ...trials, its modest efficacy and durability have created uncertainty about the impact of RTS,S immunization (when used alone) on global malaria transmission. Here we describe the development and characterization of a novel modified vaccinia virus Ankara (MVA)-based malaria vaccine which co-expresses the Plasmodium yoelii circumsporozoite protein (CSP) and IL-15. Vaccination/challenge studies showed that C57BL/6 mice immunized with the MVA-CSP/IL15 vaccine were protected significantly better against a P. yoelii 17XNL sporozoite challenge than either mice immunized with an MVA vaccine expressing only CSP or naïve controls. Importantly, the levels of total anti-CSP IgG were elevated about 100-fold for the MVA-CSP/IL15 immunized group compared to mice immunized with the MVA-CSP construct that does not express IL-15. Among the IgG subtypes, the IL-15 expressing MVA-CSP vaccine induced levels of IgG1 (8 fold) and IgG2b (80 fold) higher than the MVA-CSP construct. The significantly enhanced humoral responses and protection detected after immunization with the MVA-CSP/IL15 vaccine suggest that this IL-15 expressing MVA construct could be considered in the development of future malaria immunization strategies.
Prescribing antibiotics is a demanding and complex task where decision-making skills are of critical importance to minimize the risk of antimicrobial resistance. Despite its importance, little is ...known about the decision-making skills and cognitive strategies new Nurse Practitioners (NPs) use when prescribing antibiotics.
To identify the cognitive demands of antibiotic prescribing complexity and to explore the cognitive strategies that new NPs in New Zealand use when prescribing antibiotics.
A qualitative approach using Applied Cognitive Task Analysis (ACTA) methodology.
A purposive sample was recruited consisting of five NPs who had been registered within the last five years and were prescribing antibiotics as part of their scope of practice.
In-depth face-to-face interviews consisting of a task diagram interview and a knowledge audit were conducted and analyzed following the ACTA protocol.
Four cognitive elements were identified from the data which showed the cognitive demands of prescribing antibiotics, and the cues and strategies NPs use for safe practice. These were: 1 prescribing in the face of uncertainty (complex patients and diagnostic uncertainty); 2 making clinical decisions with insufficient/poor guidance (lack of guidelines, conflicting information); 3 producing an individualized treatment plan in view of clinical and non-clinical patient factors (patient demand/expectation, inadequate patient education, risks versus benefits of antibiotic treatment); 4 ensuring treatment efficacy and continuity of care (ineffective treatment, patient care follow up).
The ACTA framework has given insight into the current antibiotic prescribing practice of new NPs, identifying areas where professional development courses and treatment resources can be targeted to support antibiotic prescribing. NPs are likely to benefit from resources that are freely available and reflect national or local antimicrobial data. Further work is also warranted to determine whether targeted education resources and clinical pathways will help with diagnostic uncertainty, and how this could be embedded into existing curricula.
This article analyzes the environment of birth places, considering the presence of PCP room (Prepartum, Childbirth, and Postpartum) in 575 hospitals that deliver in Sistema Único de Saúde (Unified ...Health System) within the scope of Rede Cegonha. The data were extracted from a survey called Avaliação da atenção ao parto e nascimento nas maternidades da Rede Cegonha (Assessment of childbirth and birth care in the Rede Cegonha maternity units), carried out in 2017 by UFMA and ENSP, in partnership with the Ministry of Health. The PCP room model combines care for parturient women in a single space, favoring the role of women and the exercise of good practices in childbirth and birth care. The information was obtained by direct observation in the services, and assessment considered the presence and adequacy of PCP rooms and their distribution according to the pre-childbirth environment, which were compared with specific characteristics of these hospitals. Collective rooms for childbirths prevail and only 16.8% of beds are PCP rooms. This picture suggests difficulties in resource management, resistance to changes and insufficiencies in institutional support, which have hampered the transition from the childbirth environment model in Brazilian hospitals. The Brazilian obstetric and neonatal field has lived a fertile period, but it is necessary to build and sustain political-institutional disposition to advance the changes.
To assess the change in individual outcomes for people with disability and complex needs after moving into newly built, individualised apartments in the community.
People with disability ...(neurological disorder or cerebral palsy) and complex needs (n = 15, aged 18-65 years) completed quantitative self-report measures over two time-points (pre-move and 6-24 months post-move). Pre-move living arrangements included group homes, residential aged care, private rentals, and living with parents. Post-move living arrangements were individualised apartments built for people with disability. Health, wellbeing, community integration, and support needs were compared across pre- and post-move timepoints.
Paired sample t-tests showed significant improvements consistent with large effects in wellbeing (p = 0.031, Eta
2
=0.29) and community integration (p = 0.008, Eta
2
=0.41), particularly home integration, and a trend towards improved health (p = 0.077, Eta
2
=0.21). A Wilcoxon signed rank test demonstrated a trend towards reduced support needs (z= −1.941, p = 0.052) consistent with a medium effect (r = 0.35) and an average decrease of 2.4 support hours per participant per day.
Well-located housing with appropriate design, technology and support provision makes a positive contribution to wellbeing, community integration, and health for people with complex disability.
Implications for rehabilitation
People with disability who move into individualised apartments experience significant positive change in health, wellbeing, and participation.
Findings highlight the benefits of housing that foster independence and enable personal choice and control.
Evidence suggests that investment in appropriately designed and well-located housing has positive outcomes for people with disability.
Evidence collected within this outcome framework has the potential to ensure models of housing and support that are responsive to the diverse and changing needs of people with disability.
: The typical appearance of the clinical features of schizophrenia during late adolescence or early adulthood suggests that adolescence‐related neurodevelopmental events may contribute to the ...pathophysiology of this disorder. Here the role that GABA‐mediated inhibition in the dorsal lateral prefrontal cortex (DLPFC) plays in regulating working memory, a core cognitive process that matures late and that is disturbed in schizophrenia, is reviewed. Recent studies are summarized that demonstrate (1) that certain pre‐ and postsynaptic markers of GABA neurotransmission in the monkey DLPFC exhibit striking changes during adolescence, and (2) that these same markers are markedly altered in the DLPFC of subjects with schizophrenia. The implications of these findings for treatment and prevention strategies are discussed.
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