Research suggests that appearance-focused messages and exaggerated depictions of sexual activity in the media negatively influence adolescents’ body and sexual self-perceptions. As adolescents increasingly use the Internet to explore their sexuality, health risks related to online behaviors should be identified.

This 4-wave study examined the prevalence and development of 2 receptive and 2 interactive sex-related online behaviors and their relations with adolescents’ body and sexual self-perceptions. It further investigated which parental strategies regarding Internet use may reduce risky sex-related online behaviors. (Read the full article)

Maternal depression has been associated with adolescent engagement in risky behaviors such as substance use. However, there is a lack of longitudinal research examining timing-specific effects in this relationship.

The results of this study indicate that youth exposed to increasing levels of maternal depressive symptoms in middle childhood are more likely to engage in substance use and delinquent behaviors and have an earlier debut age of these behaviors. (Read the full article)

Uptake of rotavirus vaccines has increased steadily since introduction. Despite their demonstrated impact, rotavirus vaccine coverage is lower than for other vaccines recommended in infancy and disease continues to occur.

We observed higher rotavirus detection rates among patients from provider locations with lower rotavirus vaccine coverage; providers who do not offer rotavirus vaccine to age-eligible children may create pockets of susceptible children that serve as reservoirs of ongoing disease transmission. (Read the full article)

Exclusive breastfeeding until 6 months of an infant’s age is described as the safest, most powerful and cost-effective intervention to reduce infant morbidity and mortality globally. In developing countries, only ~25% of infants are exclusively breastfed for 6 months.

We developed a psycho-educational intervention combining education with techniques of cognitive-behavioral therapy, integrated it into the routine work of community health workers, which increased the rate and duration of exclusive breastfeeding until 6 months of an infant’s age. (Read the full article)

Early first sexual intercourse (FSI) is a risk factor for unplanned teenage pregnancy, sexually transmitted infection, and adverse health outcomes in adolescence and into adulthood. In girls, externalizing behaviors are more strongly associated with earlier FSI than internalizing behaviors.

Externalizing behavior from as early as 5 in boys and 10 in girls is a significant risk factor for earlier age at FSI. Internalizing behavior at ages 8 and 10 was associated with early FSI for boys but not girls. (Read the full article)

Accountable care organizations are expanding. In pediatrics, however, there is no information on cost savings or quality generated by such organizations.

Partners for Kids is a pediatric accountable care organization that increased value for Medicaid children in 34 Ohio counties, primarily through cost savings. This slowing in cost growth was achieved without diminishing the overall quality or outcomes of care. (Read the full article)

Early parenting programs benefit children’s development in low- and middle-income countries. However, the extent to which these interventions have a positive impact on parenting skills and their emotional availability is less studied.

An early child development intervention using play and communication activities to promote caregivers’ responsiveness can improve mother–child interactions, caregiving environment, caregiving practices pertaining to development and feeding, and, in combination with a nutrition intervention, support maternal emotional well-being. (Read the full article)

Clinical trials of the quadrivalent human papillomavirus vaccine show it to be highly efficacious in preventing vaccine-type–specific cervical dysplasia and anogenital warts, but few studies have assessed its effects in the real world and none have done so at the program/population level.

This study provides strong evidence of the early benefits of quadrivalent human papillomavirus vaccination on reductions in cervical dysplasia and possible reductions in anogenital warts among girls aged 14 to 17 years, offering additional justification for not delaying vaccination until girls are older. (Read the full article)

The routine childhood immunization schedule is crowded during the first 2 years, leading to deferred doses and limiting the addition of new vaccines. Combination vaccines can reduce the "shot burden" and improve coverage rates and timeliness.

Antibody response rates to antigens contained in an investigational hexavalent vaccine (DTaP5-IPV-Hib-HepB) were noninferior to licensed comparator vaccines when given as a 3-dose infant series. The safety profile was similar to control except for increased rates of mild-to-moderate, self-limited fever. (Read the full article)

Previous studies have shown that concomitant administration of the quadrivalent human papillomavirus vaccine with MCV4 and Tdap was generally well tolerated and did not interfere with the immune responses to the respective vaccines.

Concomitant administration of the novel 9-valent human papillomavirus vaccine with MCV4 and Tdap, 2 vaccines that are currently recommended for routine vaccination of adolescents, did not compromise the safety, tolerability, and immunogenicity of the individual vaccines. (Read the full article)

Executive functioning and excess weight have been associated in both cross-sectional and prospective studies, but mechanisms explaining this relationship are unclear.

Impulsivity and planning at age 10 predicted age 10 to 16 BMI changes, and age 12 binge-eating tendencies mediated the relation between impulsivity at age 10 and changes in BMI change through age 16. (Read the full article)

De novo mutations of the sodium channel gene SCN1A are the major cause of Dravet syndrome, an infantile-onset epileptic encephalopathy. The incidence of this genetic disorder in the United States is unclear.

Dravet syndrome due to SCN1A mutation is twice as common in the United States as previously thought. Genetic testing should be considered in children with ≥2 prolonged febrile seizures by 1 year of age. (Read the full article)

Lisa Dahlkvist's penalty won Sweden an Olympic shoot-out against favourites the United States, and Germany forged on, but France did not make it to the last four.

A health expert discusses what late joiner penalties are and how to avoid them.

Minister of Finance Tito Mboweni has announced a number of "exceptional tax measures as part of the fiscal package outlined by President Cyril Ramaphosa to fight the coronavirus pandemic.

A South African working abroad, able to save R36 000 per month, hopeful that he will continue these earnings, seeks the best investment strategy. Investment expert Elian Wiener responds.

A Fin24 reader who bought a property in December 2019 sent his registration papers off just before the lockdown was announced, which was unfortunately too late. A property law expert responds.

If you contracted the coronavirus at work, you may be able to claim for temporary or permanent disability, depending on how you were affected - but you will have to prove that you did, in fact, become ill at work.

The developer, Ndemic Creations, wants to remind people that Plague Inc. is just a game, not a scientific model. The game's popularity has skyrocketed amid the ongoing coronavirus outbreak, which has managed to spread to the US.

Microsoft notes it can pay bug bounty participants more than $20,000, depending on the vulnerability's severity and the report's quality. Just make sure you don't use the flaw on unsuspecting users.

So, how do we manage? What do we do when consistently engaging in the difficult discussion about rape culture is hard on our hearts, but helpful for our students?

Men were also more likely to request a transfer to a school with a male principal.

Do you have a good idea for teaching civics? Share it with us and we’ll post the best ideas online.

Very carefully, experts say, while understanding that federal laws governing special education were not written with online education in mind.

Track where schools are closed and their status for reopening.

Professor of Chemistry Paul Cremer is developing a biosensor platform that could be used to perform real-time, continuous detection of SARS-CoV-2, the virus that causes COVID-19.

The brightest tech stars, past and present, have chronicled their journeys in book form. Here are some of the best.

Replicate a crucial Andrey Arshavin strike from FC Zenit St Petersburg's UEFA Cup-winning season.

Many outside PD opportunities still separate the "haves" from the "have-nots" and uphold systemic oppression.

A growing number of students have experienced a brain injury that could affect their ability to learn in school. Yet most teachers aren't prepared to work with these students.

To help ease the transition to remote instruction, educators have launched virtual professional learning communities to share resources, ask questions, and give advice.

The heads of Deutsche Bank and Siemens, two of Germany’s biggest companies, are among a dwindling number of high-profile delegates still scheduled to attend an investment conference in Saudi Arabia following the disappearance of dissident journalist Jamal Khashoggi.

Allon Raiz is CEO of business incubator Raizcorp. In this series of articles, he offers entrepreneurs advice on surviving a crisis.

Stokvels are an important strategy for financial survival, so it's crucial to find a way to make them work during the pandemic, says Dr Norman Chivasa.

Now, more than ever, we need to be listening for market signals and ensuring that our businesses are primed to both take advantage of opportunities and to mitigate risks, says Allon Raiz.

Authorities unable or unwilling to face up to a reality that might reveal their own shortcomings and ineptitude, usually resort to pinpointing a scapegoat. This year, Covid-19 fits that bill, says Terry Bell.

As editor Wilhelm Crous puts it, "We haven't seen this movie before."

The future choices made by airlines matter a great deal for the oil market, say Liam Denning and Brooke Sutherland.

Strategic partnerships could be used to create win-win outcomes, says Sifiso Skenjana.

To history buffs, the Covid-19 pandemic must seem eerily familiar, says Noah Smith.

Argentina is a case study in what happens when an economy already on its knees implements an aggressive lockdown, says Mac Margolis.

All this foreign involvement has failed to prevent the recent coup or stabilize its aftermath. BINUCA has not been able to implement a disarmament, demobilisation and reintegration program, and it failed to convince Bozizé’s regime to reform the security sector or consolidate the peace. ECCAS has been unable to restore order in one of the smallest capitals of Africa, and troop-contributing countries have proved unable to deliver the 600 extra soldiers they committed to provide in April. Paradoxically, France, while securing Bangui’s airport, is also hosting ousted president Bozizé, who declared from exile in Paris his wish to retake power by force with the “support” of private actors.

Alors qu’une tentative de coup d’Etat contre Pierre Nkurunziza, émanant de l’ex-chef d’état-major, Godefroid Niyombaré, est en cours au Burundi, Thierry Vircoulon chercheur à l'International Crisis Group, explique qui est le général putschiste et analyse, plus généralement, l'appareil sécuritaire du Burundi.

Ibrexafungerp (formerly SCY-078) is a semisynthetic triterpenoid and potent (1->3)-β-D-glucan synthase inhibitor. We investigated the in vitro activity, pharmacokinetics, and in vivo efficacy of ibrexafungerp (SCY) alone and in combination with anti-mould triazole isavuconazole (ISA) against invasive pulmonary aspergillosis (IPA). The combination of ibrexafungerp and isavuconazole in in vitro studies resulted in an additive and synergistic interactions against Aspergillus spp. Plasma concentration-time curves of ibrexafungerp were compatible with linear dose proportional profile. In vivo efficacy was studied in a well established persistently neutropenic NZW rabbit model of experimental IPA. Treatment groups included untreated rabbits (UC) and rabbits receiving ibrexafungerp at 2.5(SCY2.5) and 7.5(SCY7.5) mg/kg/day, isavuconazole at 40(ISA40) mg/kg/day, or combinations of SCY2.5+ISA40 and SCY7.5+ISA40. The combination of SCY+ISA produced in vitro synergistic interaction. There was significant in vivo reduction of residual fungal burden, lung weights, and pulmonary infarct scores in SCY2.5+ISA40, SCY7.5+ISA40, and ISA40-treatment groups vs that of SCY2.5-treated, SCY7.5-treated and UC (p<0.01). Rabbits treated with SCY2.5+ISA40 and SCY7.5+ISA40 had prolonged survival in comparison to that of SCY2.5-, SCY7.5-, ISA40-treated or UC (p<0.05). Serum GMI and (1->3)-β-D-glucan levels significantly declined in animals treated with the combination of SCY7.5+ISA40 in comparison to those treated with SCY7.5 or ISA40 (p<0.05). Ibrexafungerp and isavuconazole combination demonstrated prolonged survival, decreased pulmonary injury, reduced residual fungal burden, lower GMI and (1->3)-β-D-glucan levels in comparison to those of single therapy for treatment of IPA. These findings provide an experimental foundation for clinical evaluation of the combination of ibrexafungerp and an anti-mould triazole for treatment of IPA.

Resistance to amoxicillin-clavulanate, a widely used beta-lactam/beta-lactamase inhibitor combination antibiotic, is rising globally, yet susceptibility testing remains challenging. To test whether whole-genome sequencing (WGS) could provide a more reliable assessment of susceptibility than traditional methods, we predicted resistance from WGS for 976 E. coli bloodstream infection isolates from Oxfordshire, UK, comparing against phenotypes from the BD Phoenix (calibrated against EUCAST guidelines). 339/976 (35%) isolates were amoxicillin-clavulanate resistant. Predictions based solely on beta-lactamase presence/absence performed poorly (sensitivity 23% (78/339)) but improved when genetic features associated with penicillinase hyper-production (e.g. promoter mutations, copy number estimates) were considered (sensitivity 82% (277/339); p<0.0001). Most discrepancies occurred in isolates with peri-breakpoint MICs. We investigated two potential causes; the phenotypic reference and the binary resistant/susceptible classification. We performed reference standard, replicated phenotyping in a random stratified subsample of 261/976 (27%) isolates using agar dilution, following both EUCAST and CLSI guidelines, which use different clavulanate concentrations. As well as disagreeing with each other, neither agar dilution phenotype aligned perfectly with genetic features. A random-effects model investigating associations between genetic features and MICs showed that some genetic features had small, variable and additive effects, resulting in variable resistance classification. Using model fixed-effects to predict MICs for the non-agar dilution isolates, predicted MICs were in essential agreement (±1 doubling dilution) with observed (BD Phoenix) MICs for 691/715 (97%) isolates. This suggests amoxicillin-clavulanate resistance in E. coli is quantitative, rather than qualitative, explaining the poorly reproducible binary (resistant/susceptible) phenotypes and suboptimal concordance between different phenotypic methods and with WGS-based predictions.

Chromosomal and plasmid-borne AmpC cephalosporinases are a major resistance mechanism to β-lactams in Enterobacteriaceae and Pseudomonas aeruginosa. The new β-lactamase inhibitor avibactam effectively inhibits class C enzymes and can fully restore ceftazidime susceptibility. The conserved amino acid residue Asn³⁴⁶ of AmpC cephalosporinases directly interacts with the avibactam sulfonate. Disruption of this interaction caused by the N³⁴⁶Y amino acid substitution in Citrobacter freundii AmpC was previously shown to confer resistance to the ceftazidime-avibactam combination (CAZ-AVI). The aim of this study was to phenotypically and biochemically characterize the consequences of the N³⁴⁶Y substitution in various AmpC backgrounds. Introduction of N³⁴⁶Y into Enterobacter cloacae AmpC (AmpC_cloacae), plasmid-mediated DHA-1, and P. aeruginosa PDC-5, led to 270-, 12,000-, and 79-fold decreases in the inhibitory efficacy (k₂/K_i) of avibactam, respectively. The kinetic parameters of AmpC_cloacaeand DHA-1 for ceftazidime hydrolysis were moderately affected by the substitution. Accordingly, AmpC_cloacaeand DHA-1 harboring N³⁴⁶Y conferred CAZ-AVI resistance (MIC of ceftazidime of 16 µg/ml in the presence of 4 µg/ml of avibactam). In contrast, production of PDC-5 N³⁴⁶Y was associated with a lower MIC (4 µg/ml) since this β-lactamase retained a higher inactivation efficacy by avibactam in comparison to AmpC_cloacaeN³⁴⁶Y. For FOX-3, the I³⁴⁶Y substitution did not reduce the inactivation efficacy of avibactam and the substitution was highly deleterious for β-lactam hydrolysis, including ceftazidime, preventing CAZ-AVI resistance. Since AmpC_cloacaeand DHA-1 display substantial sequence diversity, our results suggest that loss of hydrogen interaction between Asn³⁴⁶ and avibactam could be a common mechanism of acquisition of CAZ-AVI resistance.

Durlobactam (DUR, also known as ETX2514) is a novel β-lactamase inhibitor with broad activity against Ambler class A, C, and D β-lactamases. Addition of DUR to sulbactam (SUL) in vitro restores SUL activity against clinical isolates of Acinetobacter baumannii. The safety and pharmacokinetics (PK) of DUR alone and with SUL and/or imipenem/cilastatin (IMI/CIL) were evaluated in healthy subjects. This was a randomized, placebo-controlled study. In Part A, subjects including an elderly cohort (DUR 1 g) received single ascending doses of DUR 0.25-8 g. In Part B, multiple ascending dose of DUR 0.25-2 g were administered every 6 hours (q6h) for 29 doses. In Parts C and D, the drug-drug interaction (DDI) potential, including safety, of DUR (1 g) with SUL (1 g) and/or IMI/CIL (0.5/0.5 g) was investigated after single and multiple doses. Plasma and urine concentrations of DUR, SUL, and IMI/CIL were determined. Among 124 subjects, DUR was generally safe and well tolerated either alone or in combination with SUL and/or IMI/CIL. After single and multiple doses, DUR demonstrated linear dose proportional exposure across the studied dose ranges. Renal excretion was a predominant clearance mechanism. No drug:drug interaction potential was identified between DUR and SUL and/or IMI/CIL. SUL-DUR, 1 g (of each component) administered q6h with a 3 hour IV infusion, is under development for the treatment of serious infections due to A. baumannii.

Ceftazidime–avibactam and cefiderocol are two of the latest generation β-lactam agents that possess expanded activity against highly drug-resistant bacteria, including carbapenem-resistant Enterobacterales. Here we show that structural changes in AmpC β-lactamases can confer reduced susceptibility to both agents. A multidrug-resistant Enterobacter cloacae clinical strain (Ent385) was found to be resistant to ceftazidime–avibactam and cefiderocol without prior exposure to either agent. The AmpC β-lactamase of Ent385 (AmpC^Ent385) contained an alanine–proline deletion at positions 294–295 (A294_P295del) in the R2 loop. AmpC^Ent385 conferred reduced susceptibility to ceftazidime–avibactam and cefiderocol when cloned into Escherichia coli TOP10. Purified AmpC^Ent385 showed increased hydrolysis of ceftazidime and cefiderocol compared with AmpC^Ent385Rev, in which the deletion was reverted. Comparisons of crystal structures of AmpC^Ent385 and AmpC^P99, the canonical AmpC of E. cloacae, revealed that the two-residue deletion in AmpC^Ent385 induced drastic structural changes of the H-9 and H-10 helices and the R2 loop, which accounted for the increased hydrolysis of ceftazidime and cefiderocol. The potential for a single mutation in ampC to confer reduced susceptibility to both ceftazidime–avibactam and cefiderocol requires close monitoring.

Importance Ceftazidime–avibactam and cefiderocol are newly approved β-lactam agents that possess broad spectrum activity against multidrug-resistant (MDR) Gram-negative bacteria. We show here that a two amino-acid deletion in the chromosomal AmpC β-lactamase, identified in a clinical strain of Enterobacter cloacae, confers reduced susceptibility to both agents. By crystallographic studies of free and drug-bound forms of enzyme, we demonstrate that this deletion in AmpC induces slanting of the H-9 helix that is directly connected with the R2 loop, and disappearance of the H-10 helix, is directly responsible for increased hydrolysis of ceftazidime and cefiderocol. These findings provide novel insights into how MDR Gram-negative bacteria may evolve their β-lactamases to survive selective pressure from these newly developed β-lactam agents.