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The development of new medicines for systemic lupus erythematosus (SLE) has not addressed unmet clinical need, with only three drugs receiving regulatory approval for SLE in the last 60 years, one of which was specifically licensed for lupus nephritis. In the last 20 years it has become clear that activation of type 1 interferons (IFN) is reproducibly detected in the majority of SLE patients, and the actions of IFN in the immune system and on target tissues is consistent with a pathogenic role in SLE. These findings led to considerable drug discovery activity, first with agents directly targeting IFN family cytokines, with results that were encouraging but underwhelming. In contrast, targeting the type I IFN receptor with the monoclonal antibody anifrolumab, thereby blocking all IFN family members, was effective in a phase II clinical trial. This led to a pair of phase III trials, one of which was negative and the other positive, reflecting the difficulty of obtaining outcomes from trials in this complex disease. Nonetheless, the balance of evidence resulted in approval of anifrolumab in multiple jurisdictions from 2021 onwards. Multiple approaches to targeting the type 1 IFN pathway have subsequently had positive phase II clinical trials, including antibodies targeting cells that produce IFN, and small molecules targeting the receptor kinase TYK2, required for IFN signalling. Despite multiple hurdles, it is clear that IFN targeting in SLE is here to stay. The story of IFN-targeting therapy in SLE has lessons for drug development overall in this disease. [ABSTRACT FROM AUTHOR]

Introduction Methods Consumer and Community Involvement Results Conclusion The Sensory Processing Measure 2 (SPM2) and the Sensory Profile 2 (SP2) are two sensory processing scales often used by occupational therapists. The SPM2 and SP2 both claim to assess aspects of children's sensory processing. This cross‐sectional study examined the convergent validity of the SPM2‐Home Form (SPM2‐HF) and Child SP2 for school‐aged neurotypical children.Thirty parents/caregivers of neurotypical children aged 7 to 12 completed the SPM2‐HF and the Child SP2 about their child. Spearman rho's correlation coefficient with bootstrapping was used to investigate the correlations among the sensory, behavioural, and quadrant scores of the Child SP2 and SPM2‐HF subscale scores.Given the topic, consumers and community members were not involved in the design, execution, or write up of the study results.Several statistically significant correlations were found between the sensory and quadrant subscales of the Child SP2 with the SPM‐HF. Strong to moderate correlations were established between the sensory subscales of the Child SP2 and the SPM2‐HF, ranging from 0.40 to 0.74 (p < 0.05). Additionally, correlations between the quadrant subscales of the Child SP2 and the subscales of the SPM2‐HF ranged from weak (0.38) to strong (0.77) correlations (p < 0.05).These results provide evidence of convergent validity between the SPM2‐HF and Child SP2 for neurotypical school‐aged children. Further research on the psychometric properties of the SPM2‐HF and Child SP2 is recommended. [ABSTRACT FROM AUTHOR]

This study evaluated the impact of different food residues on the recovery of Listeria monocytogenes and Salmonella Typhimurium from stainless steel surfaces. Food residues tested include lettuce rinsate, blended lettuce, low-fat milk, and whole milk for Listeria monocytogenes, and powdered infant formula, all-purpose flour, and whole milk dairy powder for Salmonella Typhimurium. Bacterial suspensions were inoculated on stainless steel surfaces with or without food residues and held for different time periods. Significant differences (P < 0.0001) in Salmonella Typhimurium recovery were observed between the no food residue control and all food residues over 24 hours. For Listeria monocytogenes, minimal variability in recovery was observed among food residue types, with significant differences from the no food residue control (P < 0.05) observed after 24 hours. The study also found that surface sampling can spread Listeria monocytogenes and Salmonella Typhimurium on stainless steel surfaces, suggesting that food residue type may affect microbial recovery during environmental monitoring. [ABSTRACT FROM AUTHOR]

The gold standard for facioscapulohumeral muscular dystrophy (FSHD) genetic diagnostic procedures was published in 2012. With the increasing complexity of the genetics of FSHD1 and 2, the increase of genetic testing centers, and the start of clinical trials for FSHD, it is crucial to provide an update on our knowledge of the genetic features of the FSHD loci and renew the international consensus on the molecular testing recommendations. To this end, members of the FSHD European Trial Network summarized the evidence presented during the 2022 ENMC meeting on Genetic diagnosis, clinical outcome measures, and biomarkers. The working group additionally invited genetic and clinical experts from the USA, India, Japan, Australia, South‐Africa, and Brazil to provide a global perspective. Six virtual meetings were organized to reach consensus on the minimal requirements for genetic confirmation of FSHD1 and FSHD2. Here, we present the clinical and genetic features of FSHD, specific features of FSHD1 and FSHD2, pros and cons of established and new technologies (Southern blot in combination with either linear or pulsed‐field gel electrophoresis, molecular combing, optical genome mapping, FSHD2 methylation analysis and FSHD2 genotyping), the possibilities and challenges of prenatal testing, including pre‐implantation genetic testing, and the minimal requirements and recommendations for genetic confirmation of FSHD1 and FSHD2. This consensus is expected to contribute to current clinical management and trial‐readiness for FSHD. [ABSTRACT FROM AUTHOR]

Mathematics in early years settings is often restricted to learning to count and identifying simple shapes. This is partly due to the narrow scope of many early years curricula and insufficient teacher training for exploring deeper mathematical concepts. We note that geometry is an area particularly neglected. In an innovative year-long project, a group of university-based mathematicians and early years teachers collaborated on a child-led exploration of 'patterns in nature.' The early years teachers ran the project within the setting, meeting regularly with the mathematicians to discuss potential areas of interest, and to highlight the children's mathematical thinking. We found that, with the appropriate environment and guidance, the children naturally displayed deep levels of geometrical thinking and found enjoyment and satisfaction in the exploration of mathematical ideas. We define what we mean by the term 'deep geometrical thinking' and demonstrate this by looking at three excerpts through the lens of the van Hiele levels of geometric thought, finding that the children are capable of exhibiting thought at level 3 (abstraction), more advanced than previously thought of children of this age. Using a second taxonomy we also assess the range of skills across which they are demonstrating such geometric thought. [ABSTRACT FROM AUTHOR]

To investigate if preoperative ondansetron reduces postoperative nausea associated with laparoscopic gastropexy and castration in dogs. Prospective clinical study. Twenty client-owned, healthy male dogs. Dogs were premedicated with dexmedetomidine (2–5 mcg kg–1) and methadone (0.2–0.5 mg kg–1) intramuscularly. General anesthesia was induced with propofol and maintained with an inhalant anesthetic agent. Dogs were randomized into group S (saline 0.1 mL kg–1, intravenously) or group O (ondansetron 0.2 mg kg–1, intravenously). Plasma and serum were collected before premedication and 3 hours postextubation to measure arginine vasopressin (AVP) and cortisol concentrations. Nausea scoring occurred before and 10 minutes after premedication, immediately after extubation, and at 1, 2 and 3 hours postextubation. Data were analyzed by mixed and split-plot anova with Bonferroni adjustment for the number of group comparisons. Significance was set at p < 0.05. Nausea scores increased over time at 1 (p = 0.01) and 2 (p < 0.001) hours postextubation in both groups compared with before premedication. Median nausea score (0–100 mm) for groups S and O before premedication were 2.5 and 0.5 mm, respectively. At 1 and 2 hours postextubation, group S scored 7.5 and 4.0 mm and group O scored 6.0 and 5.0 mm, respectively. No significant differences in nausea scores within or between groups were observed before premedication and 3 hours postextubation. Cortisol concentrations increased significantly 3 hours postextubation in both groups (p < 0.001) compared with before premedication, with no differences between groups. AVP concentrations showed no significant differences within or between groups. Preoperative intravenous administration of ondansetron (0.2 mg kg–1) did not impact postoperative nausea after laparoscopic gastropexy and castration. Investigation of higher doses of ondansetron on the incidence of postoperative nausea and vomiting in dogs after surgery is warranted. [ABSTRACT FROM AUTHOR]

The role of human leukocyte antigen (HLA) class I and killer immunoglobulin-like receptor molecules in mediating acute retroviral syndrome (ARS) during human immunodeficiency virus type 1 (HIV-1) infection is unclear. Among 72 sub-Saharan African adults, HLA-A*23 was associated with lower odds of ARS (adjusted odds ratio, 0.10 [95% confidence interval,.01–.48]; P =.009), which warrants further studies to explore its role on HIV-1–specific immunopathogenesis. [ABSTRACT FROM AUTHOR]

Background Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. Methods A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. Results There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available. [ABSTRACT FROM AUTHOR]

Objectives: Chronic lung disease is a recognized complication in children with HIV. Acute respiratory exacerbations (ARE) are common among this group and cause significant morbidity. Exhaled nitric oxide (eNO) is a known marker of local airway inflammation. We investigated the association between eNO and ARE, biomarkers of systemic inflammation, and the effect of azithromycin on eNO levels. Methods: Individuals aged 6–19 years with HIV‐associated chronic lung disease in Harare, Zimbabwe, were enrolled in a placebo‐controlled randomized trial investigating the effect of 48‐week azithromycin treatment on lung function and ARE. eNO levels and biomarkers were measured at inclusion and after treatment in a consecutively enrolled subset of participants. Linear regression and generalized linear models were used to study associations between eNO and ARE, biomarkers, and the effect of azithromycin on eNO levels. Results: In total, 172 participants were included in this sub‐study, 86 from the placebo group and 86 from the azithromycin group. Participants experiencing at least one ARE during follow‐up had significantly higher eNO levels at baseline than participants who did not (geometric mean ratio 1.13, 95% confidence interval [CI] 1.03–1.24, p = 0.015), adjusted for trial arm, age, sex and history of tuberculosis. Matrix metalloproteinase (MMP)‐3, ‐7, and ‐10 were significantly associated with higher baseline eNO levels. At 48 weeks, azithromycin treatment did not affect eNO levels (geometric mean ratio 0.86, 95% CI 0.72–1.03, p = 0.103). Conclusion: Higher baseline eNO levels were a risk factor for ARE. eNO was associated with proinflammatory biomarkers previously found to contribute to the development of chronic lung disease. The potential use of eNO as a marker of inflammation and risk factor for ARE in HIV‐associated chronic lung disease needs further investigation. [ABSTRACT FROM AUTHOR]

Horses and cattle have shown low susceptibility to SARS-CoV-2, and there is no evidence of experimental intraspecies transmission. Nonetheless, seropositive horses in the US and seropositive cattle in Germany and Italy have been reported. The current study investigated the prevalence of antibodies against SARS-CoV-2 in horses and cattle in Switzerland. In total, 1940 serum and plasma samples from 1110 horses and 830 cattle were screened with a species-specific ELISA based on the SARS-CoV-2 receptor-binding domain (RBD) and, in the case of suspect positive results, a surrogate virus neutralization test (sVNT) was used to demonstrate the neutralizing activity of the antibodies. Further confirmation of suspect positive samples was performed using either a pseudotype-based virus neutralization assay (PVNA; horses) or an indirect immunofluorescence test (IFA; cattle). The animals were sampled between February 2020 and December 2022. Additionally, in total, 486 bronchoalveolar lavage (BAL), oropharyngeal, nasal and rectal swab samples from horses and cattle were analyzed for the presence of SARS-CoV-2 RNA via reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Six horses (0.5%; 95% CI: 0.2–1.2%) were suspect positive via RBD-ELISA, and neutralizing antibodies were detected in two of them via confirmatory sVNT and PVNA tests. In the PVNA, the highest titers were measured against the Alpha and Delta SARS-CoV-2 variants. Fifteen cattle (1.8%; 95% CI: 1.0–3.0%) were suspect positive in RBD-ELISA; 3 of them had SARS-CoV-2-specific neutralizing antibodies in sVNT and 4 of the 15 were confirmed to be positive via IFA. All tested samples were RT-qPCR-negative. The results support the hypotheses that the prevalence of SARS-CoV-2 infections in horses and cattle in Switzerland was low up to the end of 2022. [ABSTRACT FROM AUTHOR]

Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and hyaluronan more prominent in eroded plaques. Following plaque disruption, the exposure of extracellular matrix (ECM) proteins triggers platelet adhesion and thrombus formation. In this study, the impact of differential plaque composition on platelet function and thrombus formation was investigated. Platelet adhesion, activation and thrombus formation under different shear stress conditions were assessed in response to individual proteoglycans and composites representing different plaque phenotypes. The results demonstrated that all the proteoglycans tested mediated platelet adhesion but not platelet activation, and the extent of adhesion observed was significantly lower than that observed with type I and type III collagens. Thrombus formation upon the rupture and erosion ECM composites was significantly reduced (p < 0.05) compared to relevant collagen alone, indicating that proteoglycans negatively regulate platelet collagen responses. This was supported by results demonstrating that the addition of soluble biglycan or decorin to whole blood markedly reduced thrombus formation on type I collagen (p < 0.05). Interestingly, thrombus formation upon the erosion composite displayed aspirin sensitivity, whereas the rupture composite was intensive to aspirin, having implications for current antiplatelet therapy regimes. In conclusion, differential platelet responses and antiplatelet efficacy are observed on ECM composites phenotypic of plaque rupture and erosion. Proteoglycans inhibit thrombus formation and may offer a novel plaque-specific approach to limit arterial thrombosis. [ABSTRACT FROM AUTHOR]

Chlorophyll is the major light‐absorbing pigment for plant photosynthesis. While evolution has been selected for high chlorophyll content in leaves, previous work suggests that domesticated crops grown in modern high‐density agricultural environments overinvest in chlorophyll production, thereby lowering light use and nitrogen use efficiency. To investigate the potential benefits of reducing chlorophyll levels, we created ethanol‐inducible RNAi tobacco mutants that suppress Mg‐chelatase subunit I (CHLI) with small RNA within 3 h of induction and reduce chlorophyll within 5 days in field conditions. We initiated chlorophyll reduction later in plant development to avoid the highly sensitive seedling stage and to allow young plants to have full green leaves to maximise light interception before canopy formation. This study demonstrated that leaf chlorophyll reduction >60% during seed‐filling stages increased tobacco seed nitrogen concentration by as much as 17% while canopy photosynthesis, biomass and seed yields were maintained. These results indicate that time‐specific reduction of chlorophyll could be a novel strategy that decouples the inverse relationship between yield and seed nitrogen by utilising saved nitrogen from the reduction of chlorophyll while maintaining full carbon assimilation capacity. Summary statement: Reducing chlorophyll levels in tobacco plants during seed filling stages, without compromising canopy carbon assimilation, increased seed nitrogen concentration by up to 17%, suggesting a potential strategy to improve yield and seed nitrogen content simultaneously. [ABSTRACT FROM AUTHOR]

• Technology based interventions can enhance resource access. • Best practices are needed to guide implementation of technology interventions. • Trainings and support need to consider diverse levels of user proficiency. Technology-based interventions present a promising approach to support health and wellness for older adults with a range of cognitive abilities. Technology can enhance access to interventions and support scaling of programs to reach more people. However, the use of technology for intervention delivery requires particular attention to users' needs and preferences and ensuring the materials are adaptable and supportive of a diverse range of technology proficiency levels. We share best practices based on lessons learned from the deployment of a randomized controlled trial (RCT) wherein we delivered an 8-week social engagement intervention through a video technology platform called OneClick for older adults with varying cognitive abilities. We developed a set of best practices and guidelines informed by the lessons learned through this RCT implementation. Technology-based interventions require attention to the application (e.g., video calls), system requirements (e.g., system memory, broadband internet), training (e.g., adaptability based on user competency), and support (e.g., handouts, live contact). These best practices relate to user needs; training design; personnel responsibility; structuring delivery and content; and evaluating success. These research-based best practices can guide the design, development, and implementation of technology-based interventions to support older adults with varying cognitive abilities. [ABSTRACT FROM AUTHOR]