Adjuvant requirement for successful immunization with recombinant derivatives of Plasmodium vivax merozoite surface protein-1 delivered via the intranasal route

Recently, we generated two bacterial recombinant proteins expressing 89 amino acids of the C-terminal domain of the Plasmodium vivax merozoite surface protein-1 and the hexa-histidine tag (His6MSP1(19)). One of these recombinant proteins contained also the amino acid sequence of the universal pan allelic T-cell epitope (His(6)MSP1(19)-PADRE). in the present study, we evaluated the immunogenic properties of these antigens when administered via the intra-nasal route in the presence of distinct adjuvant formulations. We found that C57BL/6 mice immunized with either recombinant proteins in the presence of the adjuvants cholera toxin (CT) or the Escherichia coli heat labile toxin ( LT) developed high and long lasting titers of specific serum antibodies. the induced immune responses reached maximum levels after three immunizing doses with a prevailing IgG1 subclass response. in contrast, mice immunized by intranasal route with His(6)MSP1(19)-PADRE in the presence of the synthetic oligonucleotides adjuvant CpG ODN 1826 developed lower antibody titers but when combined to CT, CpG addition resulted in enhanced IgG responses characterized by lower IgG1 levels. Considering the limitations of antigens formulations that can be used in humans, mucosal adjuvants can be a reliable alternative for the development of new strategies of immunization using recombinant proteins of P. vivax.Universidade Federal de São Paulo, Dept Microbiol Imunol Parasitol, Escola Paulista Med, BR-04044010 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Interdisciplinar Terapia Genica, Escola Paulista Med, BR-04044010 São Paulo, BrazilUniv São Paulo, Dept Microbiol, Inst Ciencias Biomed, São Paulo, BrazilUniv São Paulo, Dept Anal Clin & Toxicol, Fac Ciencias Farmaceut, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol Parasitol, Escola Paulista Med, BR-04044010 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Interdisciplinar Terapia Genica, Escola Paulista Med, BR-04044010 São Paulo, BrazilWeb of Scienc

Strategies used in improving and assessing the level of reporting of implementation fidelity in randomised controlled trials of palliative care complex interventions: A systematic review

BACKGROUND:Implementation fidelity is critical in evaluating effectiveness of interventions.AIM: Identifying and summarising strategies to improve and assess the level of reporting of implementation fidelity in randomised controlled trials of palliative care complex interventions.DESIGN:Systematic review.DATA SOURCES:Published and completed randomised controlled trials from 2000 to current evaluating effectiveness of specialised palliative care services on patient-centred outcomes in adult patients were examined. MEDLINE was searched from 2008 to 29 September 2015 and supplemented by randomised controlled trials identified in a 2008 systematic review.RESULTS:Altogether, 20 randomised controlled trials involving 8426 patients were reviewed using 40 subcomponents of five elements of implementation fidelity (resulting in 20 × 40 = 800 items). Over 88 strategies were identified, classified under the following elements: 'treatment design', 'training providers', 'delivery of treatment', 'receipt of treatment' and 'enactment of treatment skills'. No single overarching strategy was discovered. Strategies under 'treatment design' aimed to ensure equivalent treatment dose between and within intervention and control groups, and delivery of necessary ingredients. Ongoing 'training (of) providers' included supervision and ensuring skill acquisition. Use of treatment manuals and implementation checklists aimed to aid 'delivery of treatment'. Research teams aimed to improve 'receipt of treatment' by transmitting clear information and verifying understanding, while improving 'enactment of treatment skills' by reviewing and reinforcing prior content. Only 26% of the items received sufficient reporting; 34% were either not used or reported on.CONCLUSION:Implementation fidelity in palliative care is under-recognised. A table to collate these strategies to improve implementation fidelity in palliative care research and clinical practice is proposed

Factors associated with risk of falling among younger inpatients in a mental health setting—A systematic review

Aim: To synthesise evidence related to risk factors of falls among younger mental health inpatients age ≤ 65 years old. Background: Hospitalised patients with mental illness are at increased risk of falling. Specific risk factors for falls for younger inpatients are poorly understood. Design: Systematic review. Methods: Medline, CINAHL, APA PsycINFO, Scopus and Web of Science were searched for studies published in English till December 2022. The review followed the 2020 PRISMA checklist. Odds ratios and P values of significant risk fall factors and the frequency of factors related to circumstances of falls were extracted. Results: Nine studies were included and 95 risk factors, across seven categories were extracted. These categories included socio-demographic, fall-related factors, functional status, health and mental status, psychiatric diagnosis and assessment, medication, and staff related factors. Factors related to medication, health and mental status are most reported. Majority of the patients sustained minor or no injury from the fall and circumstances of fall vary across studies. Conclusion: Factors strongly associated with risk of falls were dizziness, use of psychotropics and antihypertensive drugs. A meta-analysis of risk factors was not possible due to different dependent variables studied, controlled confounding variables and control groups used. Relevance to clinical practice: Fall prevention is relevant to all patients in mental health settings. Approaches to fall risk assessment and management need to be better tailored to younger mental health patients in the psychiatric setting. Patient and public contribution: Patient or public contribution was not possible because of the study design

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

The mediation of humanitarianism: towards a research framework

This article examines existing research on the role of mediated narratives and images of distant suffering in cultivating moral response, identifying two central strands: Philosophically oriented accounts and empirical studies of text, audience, and production. On the basis of this critical review, we suggest a research framework that simultaneously builds on and departs from existing work, helping to expand and strengthen a program of research on the mediation of humanitarianism. This framework highlights the importance of: (a) studying mediated humanitarianism as a multisited dialectical process; (b) moving away from prescriptive normativity to studying how the mediation of humanitarianism is experienced, affected, and negotiated; and (c) “undoing” despair as the motivation and consequent impulse of critique of the mediation of humanitarianism

Context-Aware Authentication Using a Proximate Wearable Device as a Source of Trust

This disclosure describes the use of a proximate, unlocked wearable device as a dynamic mobile trusted location to enhance security and ease of use for a primary device such as a smartphone or tablet. The described techniques leverage secure short-range wireless communication between a paired, secure wearable device and the primary device. When user authentication is triggered on the primary device, it initiates a ranging session with the wearable device. If the wearable device is within range and securely unlocked, it acts as a trust signal, allowing the user to use a non-biometric factor such as a pin or passcode to access the primary device even when it is not at a trusted location set up by the user. If the wearable device is not present or secure, mandatory biometric authentication is enforced on the primary device. This provides enhanced security while also providing user convenience by conditionally adjusting authentication requirements

Genome-wide meta-analysis of common variant differences between men and women

The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency >0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P < 5 × 10−8) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across ∼115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased trait

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Microfluidic Synthesis of Functional Materials as Potential Sorbents for Water Remediation and Resource Recovery

The advance of droplet-based microfluidics has enabled compartmentalization and controlled manipulation of monodispersed emulsions with high yield and incorporation efficiency. It has become a highly exotic platform in synthesizing functional material due to the presence of two immiscible liquids and the interface between them. With its intrinsic feature in high degree of product control, advanced emulsion-based synthesis of functional material is constituted as a template for effective water remediation and resource recovery. This chapter aims to provide an overview of recent advances in microfluidic technology for environmental remediation. More specifically, the facility of microemulsion-based functional materials for water remediation is reviewed. Moreover, the removal and recovery of pollutants, such as heavy metal, dye, pharmaceuticals, etc., from aquatic environment by the applications of adsorption on functional micro/nanomaterials are unfolded with respect to its potential for wastewater purification