In vitro cultures of pupal integumental explants to bioassay insect growth regulators with ecdysteroid activity for ecdysteroid amounts and cuticle secretion

The present study evaluated the in vitro bioassay with pupal integumental explants of the mealworm Tenebrio molitor to test the activity of two types of insect growth regulators (IGRs) with ecdysteroidal action. We assessed the imidazole derivative KK-42, that is know as ecdysteroid biosynthesis inhibitor, and the dibenzoylhydrazine RH-0345 (halofenozide) that representing a novel group of IGRs with ecdysteroid agonist action. Two biological endpoint were used, namely the production of ecdysteroid hormone and cuticle secretion in vitro. Also the test was done with and without renewment of the culture medium to test the persistence of action of each compound. Essentially, RH-0345 provoked higher ecdysteroid amounts, while KK-42 a reduction. Interestingly when KK-42 was followed by RH-0345, the inhibitory effect was compensated. In parallel, the deposition of cuticle in vitro was assessed and it was clear that RH-0345 could induce apolysis premature in the integument explants with the formation of a new cuticle. Here the protein and chitin contents of the explants were tested with RH-0345 and three analogous compounds, RH-2485, RH-5992 and RH-5849

Vaccinating Girls and Boys with Different Human Papillomavirus Vaccines: Can It Optimise Population-Level Effectiveness?

<label>BACKGROUND</label>Decision-makers may consider vaccinating girls and boys with different HPV vaccines to benefit from their respective strengths; the quadrivalent (HPV4) prevents anogenital warts (AGW) whilst the bivalent (HPV2) may confer greater cross-protection. We compared, to a girls-only vaccination program with HPV4, the impact of vaccinating: 1) both genders with HPV4, and 2) boys with HPV4 and girls with HPV2.<label>METHODS</label>We used an individual-based transmission-dynamic model of heterosexual HPV infection and diseases. Our base-case scenario assumed lifelong efficacy of 100% against vaccine types, and 46,29,8,18,6% and 77,43,79,8,0% efficacy against HPV-31,-33,-45,-52,-58 for HPV4 and HPV2, respectively.<label>RESULTS</label>Assuming 70% vaccination coverage and lifelong cross-protection, vaccinating boys has little additional benefit on AGW prevention, irrespective of the vaccine used for girls. Furthermore, using HPV4 for boys and HPV2 for girls produces greater incremental reductions in SCC incidence than using HPV4 for both genders (12 vs 7 percentage points). At 50% vaccination coverage, vaccinating boys produces incremental reductions in AGW of 17 percentage points if both genders are vaccinated with HPV4, but increases female incidence by 16 percentage points if girls are switched to HPV2 (heterosexual male incidence is incrementally reduced by 24 percentage points in both scenarios). Higher incremental reductions in SCC incidence are predicted when vaccinating boys with HPV4 and girls with HPV2 versus vaccinating both genders with HPV4 (16 vs 12 percentage points). Results are sensitive to vaccination coverage and the relative duration of protection of the vaccines.<label>CONCLUSION</label>Vaccinating girls with HPV2 and boys with HPV4 can optimize SCC prevention if HPV2 has higher/longer cross-protection, but can increase AGW incidence if vaccination coverage is low among boys

Tackling the Algorithmic Control Crisis -the Technical, Legal, and Ethical Challenges of Research into Algorithmic Agents

Algorithmic agents permeate every instant of our online existence. Based on our digital profiles built from the massive surveillance of our digital existence, algorithmic agents rank search results, filter our emails, hide and show news items on social networks feeds, try to guess what products we might buy next for ourselves and for others, what movies we want to watch, and when we might be pregnant. Algorithmic agents select, filter, and recommend products, information, and people; they increasingly customize our physical environments, including the temperature and the mood

Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Older Adults: Systematic Literature Review and Meta-Analysis Using the GRADE Framework

INTRODUCTION:The mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in phase 3 clinical trials, including among older adults. To inform coronavirus disease 2019 (COVID-19) vaccine selection, this systematic literature review (SLR) and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 in older adults. METHODS: We systematically searched for relevant studies reporting COVID-19 outcomes with mRNA vaccines in older adults aged ≥ 50 years by first cross-checking relevant published SLRs. Based on the cutoff date from a previous similar SLR, we then searched the WHO COVID-19 Research Database for relevant articles published between April 9, 2022, and June 2, 2023. Outcomes of interest were SARS-CoV-2 infection, symptomatic SARS-CoV-2 infection, severe SARS-CoV-2 infection, COVID-19–related hospitalization, and COVID-19–related death following ≥ 2 vaccine doses. Random effects meta-analysis models were used to pool risk ratios (RRs) across studies. Heterogeneity was evaluated using chi-square testing. Evidence certainty was assessed per GRADE framework. RESULTS:Twenty-four non-randomized real-world studies reporting clinical outcomes with mRNA vaccines in individuals aged ≥ 50 years were included in the meta-analysis. Vaccination with mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR 0.72 [95% confidence interval (CI) 0.64‒0.80]), symptomatic SARS-CoV-2 infection (RR 0.72 [95% CI 0.62‒0.83]), severe SARS-CoV-2 infection (RR 0.67 [95% CI 0.57‒0.78]), and COVID-19–related hospitalization (RR 0.65 [95% CI 0.53‒0.79]) but not COVID-19–related death (RR 0.80 [95% CI 0.64‒1.00]) compared with BNT162b2. There was considerable heterogeneity between studies for all outcomes (I2 > 75%) except death (I2 = 0%). Multiple subgroup and sensitivity analyses excluding specific studies generally demonstrated consistent results. Certainty of evidence across outcomes was rated as low (type 3) or very low (type 4), reflecting the lack of randomized controlled trial data. CONCLUSI0N: Meta-analysis of 24 observational studies demonstrated significantly lower risk of asymptomatic, symptomatic, and severe infections and hospitalizations with the mRNA-1273 versus BNT162b2 vaccine in older adults aged ≥ 50 years