Ebola virus antibody decay-stimulation in a high proportion of survivors.

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies1-3. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013-2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a 'decay-stimulation-decay' pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77-100 days and a doubling time of 46-86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5-2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.

Communication is crucial: Lessons from COVID-19 vaccination and pregnancy.

The morbidity and mortality from COVID-19 infection are higher in pregnant women compared to their nonpregnant counterparts. As real-world evidence accumulates demonstrating there is no increased risk of adverse maternal and neonatal outcomes associated with COVID-19 vaccination during pregnancy, guidelines have evolved from a case-by-case benefit-risk decision through to clear recommendation in April 2021 for COVID-19 vaccination in pregnancy. However, vaccine hesitancy is a barrier to uptake, especially among the younger population and individuals of ethnic minority backgrounds; pregnant women have additional concerns. Trust in the importance and effectiveness of the vaccine, trust in public health agencies and science, together with good communication methods regarding the safety of COVID-19 vaccines are strong factors for vaccination acceptance in pregnancy. Lack of trust in the health system was worsened by initial knowledge gaps in the information provided about COVID-19 infection and the safety and immunogenicity of COVID-19 vaccines. This was exacerbated by access to incorrect information and misinformation to fill in those knowledge gaps, especially with the increased use of social media. To provide advice and reassurance on COVID-19 vaccine safety to pregnant women, healthcare professionals involved in their care should have the knowledge and skills to provide risk-benefit communication and would benefit from access to training in science communication. Clinical pharmacologists have the expertise to appraise and synthesize emerging pharmacovigilance data, which can inform and support risk-benefit communication by other clinicians. Information should be strategically directed at individual audiences, taking their perspectives and foundational belief systems into consideration.

A small survey of introduced Zaprionus indianus (Diptera: Drosophilidae) in orchards of the eastern United States.

The African fig fly, Zaprionus indianus (Gupta), is a generalist fruit fly that typically breeds in decaying fruits from over 70 plant species. The species has spread globally from its native range in tropical Africa, becoming an invasive pest on ripening figs in Brazil. First reported in the United States in 2005 in Florida, Z. indianus has since been documented as far north as Canada and is hypothesized to recolonize northwards from southern refugia each year. We sampled drosophilid communities over the growing season at 2 orchards in Virginia from 2020 to 2022 and 11 orchards along the East Coast during the fall of 2022 to quantify the abundance of Z. indianus relative to other drosophilids across locations, seasons, and fruit crops. Massachusetts had the northernmost population, with no Z. indianus detected in Maine and no correlation between latitude and relative abundance. Variation in Z. indianus relative abundance was high between nearby orchards and abundance was higher on peaches relative to apples within orchards. Comparisons of seasonal abundance curves between 2 Virginia orchards showed similar dynamics across years with individuals first detected around July and becoming absent around December, with peaks in late summer and mid-fall. The variation in seasonal and latitudinal abundance shown here highlights a need for broader sampling to accurately characterize the range, spread, and environmental tolerances of Z. indianus in North America.

Detection, characterization, and enrollment of donors of Ebola convalescent plasma in Sierra Leone.

BACKGROUND: Passive therapy with convalescent plasma provides an early opportunity to intervene in Ebola virus disease (EVD). Methods for field screening and selection of potential donors and quantifying plasma antibody are needed. STUDY DESIGN AND METHODS: Recombinant Ebola virus glycoprotein (EBOV GP) was formatted into immunoglobulin G-capture, competitive, and double-antigen bridging enzyme immunoassays (EIAs). EVD survivors in Freetown, Sierra Leone, were recruited as potential plasma donors and assessed locally using sera alone and/or paired sera and oral fluids (ORFs). Uninfected controls comprised unexposed Gambians and communities in Western Area, Sierra Leone. Antibody neutralization in selected sera was measured retrospectively in a pseudotype virus assay. RESULTS: A total of 115 potential donors were considered for enrollment: 110 plasma samples were concordantly reactive in the three EIAs; three were concordantly unreactive and two were reactive in two of three EIAs (98.2% agreement; 95% confidence interval [CI], 93.9%-99.8%). In 88 donors with paired ORF and plasma, G-capture EIA reactivity correlated well in the two analytes (R2 = 0.795). Plasma and ORF from 44 Gambians were unreactive. ORF samples from 338 of 339 unexposed Western Area community controls were unreactive (specificity, 99.7%; 95% CI, 98.4%-99.7%); ORF samples from 113 of 116 Kerry Town EVD survivors were reactive (sensitivity, 97.4%; 95% CI, 92.5%-99.5%). Strong reactivity in G-capture and/or competitive EIAs identified donors with high plasma EBOV GP antibody levels in the double-antigen bridging assay, correlating with high levels of neutralizing antibody. CONCLUSIONS: In-field testing can qualify convalescent donors for providing high-titer antibody.

An assessment of healthcare professionals' knowledge about and attitude towards influenza vaccination in Freetown Sierra Leone: a cross-sectional study.

BACKGROUND: Vaccinating healthcare professionals against influenza is considered an effective infection control measure. However, there is a low uptake of influenza vaccine among healthcare professionals around the globe. Currently, it is unknown whether healthcare professionals in Sierra Leone are aware of, and have been vaccinated against influenza. Also, there is a paucity of research evidence on their level of knowledge and attitude toward influenza vaccination. This study assessed healthcare professionals' current influenza vaccine uptake rate, reasons for not getting vaccinated as well as their awareness, knowledge of, and attitude towards influenza vaccination in Freetown Sierra Leone. METHOD: A cross-sectional study was conducted between February and April 2016 among healthcare providers working in four public and two private health facilities in Freetown Sierra Leone. Linear regression analysis, one-way ANOVA and independent t-test were employed for data analysis. RESULTS: Among 706 respondents that participated in the study more than half were females 378 (53.6%), nurses 425 (60.4%), and the majority were between the age group of 20-39 years 600 (85.3%). Only 46 (6.5%) were vaccinated against influenza. Key reasons for not vaccinated against influenza were less awareness about influenza vaccination among HCPs 580 (82.73%) with (ß = 0.154; CI 0.058-0.163), the high cost of influenza vaccines and therefore not normally purchased 392 (55.92%) having (ß = 0.150; CI 0.063-0.186). More than half believed that HCPs are less susceptible to influenza infections than other people. Also, majority 585 (84.3%) of HCPs thought that influenza disease could be transmitted after symptoms appear. In addition, 579 (83.2%) of HCPs felt that symptoms usually appear 8-10 days after exposure. Close to half 321 (46.0%) of HCPs were not aware of the influenza immunisation guidelines published by the Advisory Committee on Immunization Practices and Centre for Disease Control. CONCLUSION: Influenza vaccine coverage among healthcare professionals in Freetown Sierra Leone was low. High cost, inadequate knowledge about influenza and its vaccine as well as the lack of awareness of vaccine availability were key barriers. Increasing access to influenza vaccine and the use of appropriate educational interventions to increase knowledge and awareness are required to improve influenza vaccination coverage among HCPs.

Dermal Titanium Dioxide Deposition Associated With Intralesional Triamcinolone Injection.

Cutaneous discoloration secondary to dermal deposition of titanium dioxide (TiO2) particles is recognized but seldom reported in the literature. In this report, the authors describe the case of a 61-year-old gentleman, with a long history of alopecia areata, who presented with numerous, discrete dark blue macules on the scalp. Scanning electron microscopy with energy dispersive x-ray spectroscopy analysis ultimately identified the macules as deposits of TiO2. The patient had a history of intralesional triamcinolone injections for management of alopecia areata. A sample of generic 0.1% triamcinolone acetonide paste was analyzed and found to contain many TiO2 particles analogous to those seen in the patient's biopsy sample. To the authors' knowledge, this is the first reported case of TiO2 deposition in the dermis likely resulting from topical combined with intralesional triamcinolone injection.

Histopathologic evaluation of the sentinel lymph node for malignant melanoma: the unstandardized process.

Metastasis from malignant melanoma (MM) usually first presents in the draining lymph node basin and thus sentinel lymph node (SLN) biopsy is a staging tool used to predict risk of metastases and death in higher risk tumors and has become the standard of care. Differences in the processing and methods used in the histopathological examination of SLNs can affect the positivity rate for metastatic MM because isolated MM deposits may be small and variably distributed in the SLN. The examination of SLNs is not standardized. The authors surveyed institutions across the United States who process SLNs for MM to better characterize the current methods used and to suggest a standardized approach to improve the reliability of the SLN biopsy. A survey of 142 academic institutions in the United States regarding the methods used in the evaluation of the SLN biopsy for MM was conducted. Thirty-two institutions responded. Eighty-one percent of the institutions (26 of 32) had a protocol that they used for SLN examination. In regards to gross dissection, 28% of the responders (9 of 32) initially bivalve (cut the SLN in half), whereas 59% (19 of 32) use a bread loaf technique, cutting the SLN at even intervals without specifically commenting about orientation to the hilum. The number of levels initially cut from the SLN block varied from 1 to 8 levels per block. Thirty-nine percent of the respondents (12 of 31) routinely order immunohistochemistry before evaluation of the initial hematoxylin- and eosin-stained sections. Eighty percent of the respondents (24 of 30) report the maximum dimension of the metastatic tumor deposit. The response rate was low (22%), and most respondents did not indicate how many SLN accessions were performed at their institution each year. Histologic protocols for processing SLNs for MM vary among institutions. Different methods of handling SLNs result in varying sensitivities for detection of metastases. Data derived from these varied approaches to develop and determine prognostic and staging categories may be inconsistent. A standardized yet practical approach is needed to provide reliable information on which prognosis can be determined and therapeutic guidelines can be based. The hope is for dermatologists and those treating patients with MM to understand the intricacies and inconsistencies involved in performance and interpretation of this key staging tool.

Using a Brief Intervention to Improve Partner-Focused Conversation in Adolescents with Autism.

Individuals on the autism spectrum often experience pragmatic social conversation difficulties that include showing interest in their conversational partners. This may become particularly evident during adolescence when conversation with peers is the primary medium for social interaction. This study used a multiple baseline design across participants to investigate the effects of a brief intervention package on the partner-focused conversation of three adolescents with autism. Results showed increased partner-focused questions and comments for all participants. Social validity assessments indicated that the intervention led to meaningful improvements in peer conversations.

Spatial and temporal variation in abundance of introduced African fig fly (Zaprionus indianus) (Diptera: Drosophilidae) in the eastern United States.

The African fig fly, Zaprionus indianus (Gupta), has spread globally from its native range in tropical Africa, becoming an invasive crop pest in select areas such as Brazil. Z. indianus was first reported in the United States in 2005 and has since been documented as far north as Canada. As a tropical species, Z. indianus is expected to have low cold tolerance, likely limiting its ability to persist at northern latitudes. In North America, the geographic regions where Z. indianus can thrive and seasonal fluctuations in its abundance are not well understood. The purpose of this study was to characterize the temporal and spatial variation in Z. indianus abundance to better understand its invasion of the eastern United States. We sampled drosophilid communities over the growing season at two orchards in Virginia from 2020-2022 and several locations along the East Coast during the fall of 2022. Virginia abundance curves showed similar seasonal dynamics across years with individuals first detected around July and becoming absent around December. Massachusetts was the northernmost population and no Z. indianus were detected in Maine. Variation in Z. indianus relative abundance was high between nearby orchards and across different fruits within orchards but was not correlated with latitude. Fitness of wild-caught females decreased later in the season and at higher latitudes. The patterns of Z. indianus abundance shown here demonstrate an apparent susceptibility to cold and highlight a need for systematic sampling to accurately characterize the range and spread of Z. indianus.

Using Peer Supports to Encourage Adolescents With Autism Spectrum Disorder to Show Interest in Their Conversation Partners.

PURPOSE: This study was conducted to evaluate the effects of a multicomponent peer-mediated intervention (PMI) on teaching adolescents with autism spectrum disorder (ASD) how to show interest in peer conversation partners by asking partner-focused questions about the person, their interests, or their experiences and by making partner-focused comments that positively affirm peer statements or express concern. METHOD: A multiple-baseline design across three verbally fluent high school students with ASD was used to assess the effects of the PMI, which involved training peers (n = 10) to support conversation and the students' use of target skills, and training the students to use partner-focused skills with the aid of a self-reflection cue sheet during conversation with trained peers in a high school cafeteria. Ten-minute samples of student-peer conversations were transcribed and analyzed. Generalization with untrained peers was assessed. RESULTS: The PMI was highly effective in increasing all students' use of partner-focused skills. Gains were maintained by two students in a return-to-baseline condition. Generalization was evident for all students with varied results. Peers and students with ASD perceived the intervention to be beneficial. CONCLUSIONS: This study adds to the limited research showing that PMI can be used in high school settings to improve target conversational skills and provides preliminary evidence that PMI can successfully address an underresearched pragmatic language difficulty (i.e., introducing and maintaining topics of conversation of relevance and interest to conversation partners) common among adolescents with ASD. These findings invite replication to extend generality and assess the impact of the intervention on peer relationships. Supplemental Material https://doi.org/10.23641/asha.16915663.

Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3).

Ephrin receptors (Eph) affect cell shape and movement, unlike other receptor tyrosine kinases that directly affect proliferative pathways. The kinase domain of EphA3 is activated by ephrin binding and receptor oligomerization. This activation is associated with two tyrosines in the juxtamembrane region; these tyrosines are sites of autophosphorylation and interact with the active site of the kinase to modulate activity. This allosteric event has important implications both in terms of understanding signal transduction pathways mediated by Eph kinases as well as discovering specific therapeutic ligands for receptor kinases. In order to provide further details of the molecular mechanism through which the unphosphorylated juxtamembrane region blocks catalysis, we studied wild-type and site-specific mutants in detail. High-resolution structures of multiple states of EphA3 kinase with and without the juxtamembrane segment allowed us to map the coupled pathway of residues that connect the juxtamembrane segment, the activation loop, and the catalytic residues of the kinase domain. This highly conserved set of residues likely delineates a molecular recognition pathway for most of the Eph RTKs, helping to characterize the dynamic nature of these physiologically important enzymes.

The Epilepsy Risk Awareness (ERA) Scale: A New Era for Holistic Risk Assessment in Epilepsy.

Objective: Best care in epilepsy balances protecting people with epilepsy from risks and avoiding undue restrictions in order to improve quality of life. To date, no single risk assessment tool has been widely adopted by both people with epilepsy and health-care professionals such as specialist epilepsy nurses. The present research refined the Epilepsy Risk Awareness (ERA) Scale, a validated and holistic risk assessment tool, by assessing test-retest reliability of each question and incorporating suggestions from patients regarding design and content. Methods: The draft clinical scale was administered to 102 adult participants from the Epilepsy Service at the Royal Free London National Health Service (NHS) Foundation Trust on two occasions. Quantitative and qualitative analyses were conducted-intraclass correlation coefficient (ICC) estimates were used to assess test-retest reliability of questions, and thematic analysis was used to analyze participants' comments and feedback. Following analysis, the ERA Scale was amended. Of the 102 participants, 32 conducted a further review of the revised ERA Scale to test completion time and provide final comments. Results: ICC reliability level estimates varied from "poor to moderate" to "good to excellent," and four qualitative themes were identified. The ERA Scale was amended accordingly to enhance practicality and usefulness, reducing completion time to approximately 5 min. Significance: The ERA Scale is a validated tool that aims to change clinical practice by standardizing risk assessment in epilepsy, providing a holistic approach that focuses on improved safety and quality of life.

Enhancing Social Skills of Young Children With ADHD: Effects of a Sibling-Mediated Intervention.

Children with attention deficit/hyperactivity disorder (ADHD) are at risk for experiencing problems with social functioning that are associated with adverse outcomes in adolescence and adulthood. To date, the most common ADHD treatments for children, psychostimulants and adult-mediated interventions, have had limited success reducing social impairments associated with ADHD. Using a non-concurrent multiple baseline across participants design, we examined the efficacy of a sibling-mediated social intervention for reducing negative and increasing positive social behaviors of three children with ADHD. We also assessed implementation integrity by the siblings, and acceptability from the perspective of the participant with ADHD, the siblings, and the parents. Results indicated that siblings learned and used specific social skills strategies with their siblings with ADHD that lead to increases in sharing, helping, and compromising behaviors for children with ADHD compared with baseline (Tau-U = 0.9531, p < .001). Summary of findings, study limitations, implications for research, and practice are discussed.

Structural insights into the inhibited states of the Mer receptor tyrosine kinase.

The mammalian ortholog of the retroviral oncogene v-Eyk, and a receptor tyrosine kinase upstream of antiapoptotic and transforming signals, Mer (MerTK) is a mediator of the phagocytic process, being involved in retinal and immune cell clearance and platelet aggregation. Mer knockout mice are viable and are protected from epinephrine-induced pulmonary thromboembolism and ferric chloride-induced thrombosis. Mer overexpression, on the other hand, is associated with numerous carcinomas. Although Mer adaptor proteins and signaling pathways have been identified, it remains unclear how Mer initiates phagocytosis. When bound to its nucleotide cofactor, the high-resolution structure of Mer shows an autoinhibited alphaC-Glu-out conformation with insertion of an activation loop residue into the active site. Mer complexed with compound-52 (C52: 2-(2-hydroxyethylamino)-6-(3-chloroanilino)-9-isopropylpurine), a ligand identified from a focused library, retains its DFG-Asp-in and alphaC-Glu-out conformation, but acquires other conformational changes. The alphaC helix and DFGL region is closer to the hinge region and the ethanolamine moiety of C52 binds in the groove formed between Leu593 and Val601 of the P-loop, causing a compression of the active site pocket. These conformational states reveal the mechanisms of autoinhibition, the pathophysiological basis of disease-causing mutations, and a platform for the development of chemical probes.

Community survey of carer's: individual epilepsy guidelines (IEG) for rescue medication.

OBJECTIVE: To evaluate the effectiveness and viability of individual epilepsy guidelines as a user-friendly tool for carers of people with epilepsy and learning disabilities. In this paper the term carer refers to family carers and support workers. METHOD: A retrospective survey questionnaire designed to ascertain the effectiveness and feasibility of individual epilepsy guidelines as a user-friendly tool. This was evaluated for examining clinical practice improvements and service delivery. RESULTS: 44 questionnaires were mailed to carers who were supporting individuals with epilepsy. There was an overall response of 42(96%). CONCLUSION: This survey indicates that the IEG was a useful resource assisting carers with the management of emergency seizure events in the community.

An assessment of achievements of the WEEE Directive in promoting movement up the waste hierarchy: experiences in the UK.

Rapidly developing technology and an increasing number of products containing electrical or electronic functions, has led to discarded electrical and electronic equipment (EEE) being one of the fastest growing waste streams. The European Union (EU) has enacted several iterations of the Waste Electrical and Electronic Equipment (WEEE) Directive to address this complex waste stream. However, recycling dominates treatments for e-waste, despite the established 'waste hierarchy' showing waste prevention and reuse are generally preferable to recycling. This paper reports on 30 semi-structured interviews, undertaken across the EEE value chain, examining the impact of the WEEE Directive in the UK. The interviews confirmed that reuse takes place for a limited number of product types, mostly on a small scale. Additionally, whilst legislation has prompted innovation in recycling and higher capture rates, resource recovery is in practice limited to easily salvageable materials, whilst recovery of critical raw materials is often neglected. Furthermore, there is confusion around available collection networks, particularly for small WEEE, which consistently appears in residual waste streams. The waste hierarchy remains the key component of EU waste strategy and moving to the higher levels of the waste hierarchy is an essential part of achieving sustainable waste management and moving towards a circular economy. The paper proposes a series of measures to this end: promoting recovery routes and practices that facilitate reuse of suitable products, adapting recycling technology to increase recovery of critical raw materials and targeted policies to encourage the application of the waste hierarchy within a resource efficiency-oriented framework.

The crystal structure of human WD40 repeat-containing peptidylprolyl isomerase (PPWD1).

Cyclophilins comprise one of the three classes of peptidylprolyl isomerases found in all eukaryotic and prokaryotic organisms, as well as viruses. Many of the 17 annotated human cyclophilins contain the catalytic domain in tandem with other domains, and many of the specific functions of a particular cyclophilin or its associated domains remain unknown. The structure of the isomerase domain from a spliceosome-associated cyclophilin, PPWD1 (peptidylprolyl isomerase containing WD40 repeat), has been solved to 1.65 A. In the crystal, the N-terminus of one isomerase domain is bound in the active site of a neighboring isomerase molecule in a manner analogous to substrate. NMR solution studies show that this sequence binds to the active site of the cyclophilin, but cannot be turned over by the enzyme. A pseudo-substrate immediately N-terminal to the cyclophilin domain in PPWD1 could have wider implications for the function of this cyclophilin in the spliceosome, where it is located in human cells.