Skills learned in standardized courses are estimated to last only a few months. Neonatal Resuscitation Program certification is mandatory for all pediatric residents and is valid for 2 years. Exact timing of when proficiency is lost is unknown.

Neonatal Resuscitation Program skills deteriorate immediately after certification, whereas knowledge is better retained. Significant skill deficits were seen at baseline raising concerns regarding the efficacy of the current course structure. Discrepancies in knowledge and skill retention may impact caregiver performance. (Read the full article)

Critics argue that pediatric research without the potential for clinical benefit treats children as mere means to benefit others. Yet, there are no data to assess whether adolescents who participate in research, or their parents, agree with this view.

Respondents felt that by participating in research the adolescents were making important contributions to help others, and the adolescents felt proud to be doing so. These findings support the view that nonbeneficial pediatric research involves a type of charitable activity. (Read the full article)

Knowledge is limited regarding the epidemiology of persistent pulmonary hypertension of the newborn (PPHN). Previous work has implicated a host of perinatal risk factors and a few antenatal antecedents of PPHN, including maternal consumption during pregnancy of nonsteroidal antiinflammatory medications.

In contrast to results of previous studies, we found no association between PPHN and maternal consumption during late pregnancy of nonsteroidal antiinflammatory drugs in general or ibuprofen in particular. (Read the full article)

Although previous studies indicate that perinatal factors are associated with altered neurodevelopment, data on the association between ischemic-hypoxic conditions and attention-deficit/hyperactivity disorder in children are sparse.

This study demonstrates that preeclampsia, birth asphyxia, and respiratory distress syndrome are independently associated with increased risk of attention-deficit/hyperactivity disorder in a large population-based study. (Read the full article)

Educational debt is an important topic in pediatrics. Deciding on a career path is a critical personal decision, shaped by multiple factors. The relationship between educational debt and career choice is unclear.

Educational debt among graduating pediatric residents is high and continues to increase. Higher debt is one factor that may lead residents toward a career in primary care or hospitalist practice, rather than pursuing fellowship training and a subspecialist career. (Read the full article)

Bisphenol A (BPA) is an environmental endocrine disruptor that can leach from polycarbonate plastics and epoxy resins, leading to widespread exposure. Fetal and early postnatal periods are particularly vulnerable to exposure to BPA.

This study identified medical devices as a potential source of exposure to BPA among premature infants in the NICU, even when efforts to reduce polycarbonate plastics were taken. (Read the full article)

Impaired visual development has been reported in infants born to mothers prescribed methadone in pregnancy. Immature visual evoked potentials have been reported in this population, but data were confounded by gestation, growth restriction, and illicit drug use.

Visual evoked potentials are small and immature in infants exposed to methadone and other drugs of misuse in utero. These changes are independently associated with methadone exposure and persist after controlling for gestation, socioeconomic deprivation, alcohol consumption, and cigarette smoking. (Read the full article)

Children have been shown to imitate behaviors they see on screen.

Modifying what children watch can improve their observed behavior. (Read the full article)

Studies have highlighted a lack of patient awareness of potential increased cancer risks associated with computed tomography (CT) scans in adult patients and in nonurgent settings. However, little is known about parental awareness of these risks in an emergency setting.

Approximately half of parents were aware of the potential cancer risks from CT scans in an emergency setting. Although risk disclosure moderately reduced willingness to proceed with recommended testing, almost all parents preferred an informed discussion before CT imaging. (Read the full article)

Several studies have shown that behavioral problems can be associated with defecation and voiding disorders, although few studies have looked directly at a link between a diagnosis of attention-deficit/hyperactivity disorder (ADHD) and constipation or fecal incontinence.

We identified an increased risk for both constipation and fecal incontinence in children with ADHD. In patients with concomitant ADHD and defecation disorders, more aggressive medical and behavioral treatment of the constipation or fecal incontinence may be warranted. (Read the full article)

Certain characteristics of the sleep environment increase the risk for sleep-related, sudden, and unexplained infant death. These characteristics have the potential to generate asphyxia. The relationship between the deaths occurring in these environments and neurochemical abnormalities in the brainstem that may impair protective responses to asphyxia is unknown.

We report neurochemical brainstem abnormalities underlying cases of sudden infant death that are associated with and without potential asphyxial situations in the sleep environment at death. The means to detect and treat these abnormalities in infants at risk are needed. (Read the full article)

Attention-deficit/hyperactivity disorder (ADHD) is the most common mental health condition diagnosed in childhood, is highly heritable, and more common in boys. Although studies have identified perinatal risk factors, no one has investigated perinatal risk factors separately in boys and girls.

Contrary to other studies, low birth weight, postterm pregnancy, low Apgar scores, and fetal distress were not risk factors for ADHD irrespective of gender. Early term deliveries increased the risk of ADHD, and oxytocin augmentation in girls may be protective. (Read the full article)

The demand for donor kidneys for transplantation exceeds supply. En bloc kidney transplantation and donation after determination of circulatory death from pediatric donors increases the potential donor pool.

Newborn infants undergoing elective withdrawal of life support in the NICU are a previously unrecognized source of potential kidney donors. (Read the full article)

Injuries sustained by children in the school setting have a significant public health impact. A concerning subgroup of school injuries are due to intentional and violent etiologies. Several studies have identified a need for further research to understand intentional school-based injuries.

This study discusses national estimates and trends over time and risk factors of intentional injury–related emergency department visits due to injuries sustained in the school setting. (Read the full article)

Research indicates that bullying, a type of peer victimization, is related to worse mental and physical health. Most previous studies have been cross-sectional and have not examined effects of bullying over time.

This analysis examined longitudinal effects of bullying on mental and physical health from middle school to high school. Experiencing chronic bullying, especially in both the past and present, was associated with worse psychological and physical health. (Read the full article)

Approximately 50% of children diagnosed with attention-deficit/hyperactivity disorder (ADHD) at <7 years of age in the community do not meet criteria for ADHD over time. There is a need to examine predictors of diagnostic stability in young children with ADHD.

Predictors of diagnostic stability from early to middle childhood include child’s baseline externalizing and internalizing symptoms, parental history of psychopathology, and socioeconomic status. These predictors may guide treatment planning at the time of ADHD diagnosis. (Read the full article)

Childhood attention-deficit/hyperactivity disorder has been associated with both childhood and adult obesity, whereas treatment with stimulants has been associated with delayed child growth. No longitudinal studies with details about dates of diagnosis, treatment, and duration of stimulant use have been published.

Using electronic health record data, this was the first study to evaluate the independent associations of attention-deficit/hyperactivity disorder diagnosis, stimulant treatment, age at first stimulant use, and duration of stimulant use on longitudinal BMI trajectories throughout childhood and adolescence. (Read the full article)

Up to 50% of children with attention-deficit/hyperactivity disorder (ADHD) meet criteria for a comorbid anxiety disorder. Despite the high prevalence of anxiety in these children, the impact of anxiety on the lives of children with ADHD has been largely overlooked.

Presence of ≥2 anxiety comorbidities in children with ADHD was associated with poorer child quality of life, daily functioning, and behavior. Multiple anxiety comorbidities were associated with poorer functioning for children with both ADHD-Inattentive and ADHD-Combined presentation. (Read the full article)

Messages emphasizing societal benefits of vaccines have been linked to increased vaccination intentions in adults. It is unclear if this pattern holds for parents deciding whether to vaccinate their children.

Findings suggest that health care providers should emphasize the direct benefits of MMR vaccination to the child. Mentioning societal benefits seems to neither add value to, nor interfere with, information highlighting benefits directly to the child. (Read the full article)

Sleep disorders are common in children and adolescents and have a substantial negative impact on daily life and school performance. Long-term evaluations of the efficacy and safety of pharmacologic treatment options for sleep disorders are lacking in pediatric patients.

These 2 studies provide the first evaluation of the effectiveness and safety of eszopiclone in children and adolescents with insomnia associated with ADHD. Data presented here encompass longer-term (up to 1 year) pediatric exposure to eszopiclone. (Read the full article)

Obesity among youth can have immediate health effects as well as longer-term consequences during adulthood. Overweight/obese children and adolescents are much more likely than normal-weight children to become overweight/obese adults.

This large, multisite longitudinal study examines patterns of exit from and entry into obesity between childhood and adolescence. Socioeconomic factors, body image, television habits, and parental obesity were important predictors of whether children remained obese or became obese. (Read the full article)

Hospitalized pediatric patients are often exposed to many medications during an inpatient admission. Drug–drug interactions may increase the risk of developing medication-related adverse drug events, leading to serious clinical morbidity and mortality.

Exposure to "major" potential drug–drug interactions occurs in 41% of pediatric hospitalizations in children’s hospitals. One-half of all these exposures were due to less common specific drug pairs (≤3% of patients exposed per hospital day) and thus may be less clinically familiar. (Read the full article)

Light and intermittent smoking are harmful, but increasingly common, smoking patterns. It is unknown how adolescents perceive these smoking patterns, and whether these views differ by sociodemographic characteristics, and exposure to and use of tobacco.

US adolescents perceive light and intermittent smoking as significantly less dangerous than heavier smoking. One in 4 adolescents believes intermittent smoking causes little to no harm. Perceptions of relative safety were common among smokers. (Read the full article)

Menu labels depicting physical activity calorie equivalents may lead to ordering of fast food meals totaling fewer calories for adults. The effects of physical activity calorie equivalent labeling on parents’ fast food decisions for their children have not been examined.

Parents shown menus with any type of caloric content label may order fast food meals totaling fewer calories for their children. Menu labels showing physical activity equivalents may be more likely to influence parents to encourage their children to exercise. (Read the full article)

Attention is a prerequisite for neurocognitive and behavioral functioning, having a crucial role in academic and social child development. Children with traumatic brain injury have pronounced deficits in attention, but the nature and consequences of these deficits remain unclear.

Lapses of attention represent a core attention deficit after pediatric mild traumatic brain injury with risk factors for complicated traumatic brain injury, or moderate/severe traumatic brain injury. Importantly, lapses of attention explain the relation between intelligence and parent-rated attention problems. (Read the full article)

Infants born very prematurely or with a very low birth weight are known to have an increased risk of attention-deficit/hyperactivity disorder (ADHD). Results concerning late preterm children are controversial and studies examining fetal growth represented by weight for gestational age are scarce.

We demonstrate that each declining week of gestation increases the risk of ADHD. Also, late preterm infants have an increased risk. Furthermore, as weight for gestational age becomes smaller than 1 SD below the mean, the risk of ADHD increases. (Read the full article)

Many studies have suggested that autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are commonly co-occuring neurodevelopmental conditions.

In children with co-occurring ASD and ADHD, an initial ADHD diagnosis may be associated with delayed ASD diagnosis and a higher likelihood of ASD diagnosis older than 6 years of age. Clinicians should consider ASD when evaluating young children presenting with ADHD symptoms. (Read the full article)

An educator's experience teaching math is important, but performance on math-content-certification tests is the best predictor of how well a teacher's students will perform in early algebra, finds a new study by the Regional Educational Laboratory Central at Marzano Research.

Sony has been granted a patent for a new PlayStation controller that features two more buttons than the existing DualShock 4 model, but don't look for it with the PS5.

Digital curricula repositories are helping to fill the growing need for more and better multimedia content.

This article, published ahead of print on 28 July 2008, has been withdrawn by the authors. Although moderate synergy between P2-RANTES and C peptides can be observed with high statistical significance in cell fusion assays, this synergy was not able to be verified in HIV viral assays. The authors regret the overstatement of synergy and will revise the paper for publication at a later date.

Leishmania major is the causative agent of cutaneous leishmaniasis (CL). No human vaccine is available for CL and current drug regimens present several drawbacks such as emerging resistance, severe toxicity, medium effectiveness, and/or high cost. Thus, the need for better treatment options against CL is a priority. In the present study, we validate the enzyme methionine aminopeptidase-1 (MetAP1), a metalloprotease that catalyzes the removal of N-terminal methionine from peptides and proteins, as a chemotherapeutic target against CL infection. The in vitro antileishmanial activity of eight novel MetAP1 inhibitors (OJT001-OJT008) were investigated. Three compounds OJT006, OJT007, and OJT008 demonstrated potent anti-proliferative effect in macrophages infected with L. major amastigotes and promastigotes at submicromolar concentrations, with no cytotoxicity against host cells. Importantly, the leishmanicidal effect was diminished by almost 10-fold in transgenic L. major promastigotes overexpressing MetAP1_LM in comparison to wild-type promastigotes. Furthermore, the in vivo activity of OJT006, OJT007, and OJT008 were investigated in L. major-infected BALB/c mice. In comparison to the control group, OJT008 significantly decreased footpad parasite load by 86%, and exhibited no toxicity against in treated mice. We propose MetAP1 inhibitor OJT008 as a potential chemotherapeutic candidate against CL infection caused by L. major infection.

Lipid II is an essential precursor of the bacterial cell wall biosynthesis and thereby an important target for various antibiotics. Several lanthionine-containing peptide antibiotics target lipid II with lanthionine-stabilized lipid II-binding motifs. Here, we used the biosynthesis system of the lantibiotic nisin to synthesize a two lipid II binding motifs-containing lantibiotic, termed TL19, which contains the N-terminal lipid II binding motif of nisin and the distinct C-terminal lipid II binding motif of one peptide of the two-component haloduracin (i.e. HalA1). Further characterization demonstrated that (i) TL19 exerts 64-fold stronger antimicrobial activity against E. faecium than nisin (1-22), which has only one lipid II binding site, and (ii) both the N- and C-terminal domains are essential for the potent antimicrobial activity of TL19, as evidenced by mutagenesis of each single and double domains. These results show the feasibility of a new approach to synthesize potent lantibiotics with two different lipid II binding motifs to treat specific antibiotic-resistant pathogens.

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.

There is an urgent need for new, potent anti-tuberculosis (TB) drugs with novel mechanisms of action that can be included in new regimens to shorten the treatment period for TB. After screening a library of carbostyrils, we optimized 3, 4-dihydrocarbostyril derivatives and identified OPC-167832 as having potent anti-tuberculosis activity. The minimum inhibitory concentrations of the compound for Mycobacterium tuberculosis ranged from 0.00024 to 0.002 μg/mL. It had bactericidal activity against both growing and intracellular bacilli, and the frequency of spontaneous resistance for Mycobacterium tuberculosis H37Rv was less than 1.91 x 10^-7. It did not show antagonistic effects with other anti-TB agents in an in vitro checkerboard assay. Whole genome and targeted sequencing of resistant isolates to OPC-167832 identified the decaprenylphosphoryl-β-D-ribose 2'-oxidase (DprE1), an essential enzyme for cell wall biosynthesis, as the target of this compound, and further studies demonstrated inhibition of the DprE1 enzymatic activity by OPC-167832. In a mouse model of chronic TB, OPC-167832 showed potent bactericidal activities starting at a dose of 0.625 mg/kg. Further, it exhibited significant combination effects in 2-drug combinations with delamanid, bedaquiline, or levofloxacin. Finally, 3-4 drug regimens comprised of delamanid and OPC-167832 as the core along with bedaquiline, moxifloxacin, or linezolid showed superior efficacy in reducing bacterial burden and preventing relapse compared to the standard treatment regimen. In summary, these results suggest that OPC-167832 is a novel and potent anti-TB agent and regimens containing OPC-167832 and new or repurposed anti-TB drugs may have the potential to shorten the duration of treatment for TB.

The human diseases caused by the fungal pathogens Cryptococcus neoformans and C. gattii are associated with high indices of mortality, and toxic and/or cost-prohibitive therapeutic protocols. The need for affordable antifungals to combat cryptococcal disease is unquestionable. Previous studies suggested benzimidazoles as promising anti-cryptococcal agents combining low cost and high antifungal efficacy, but their therapeutic potential has not been demonstrated so far. In this study, we investigated the antifungal potential of fenbendazole, the most effective anti-cryptococcal benzimidazole. Fenbendazole was inhibitory against 17 different isolates of C. neoformans and C. gattii at a low concentration. The mechanism of anti-cryptococcal activity of fenbendazole involved microtubule disorganization, as previously described for human parasites. In combination with fenbendazole, the concentrations of the standard antifungal amphotericin B required to control cryptococcal growth were lower than those required when this antifungal was used alone. Fenbendazole was not toxic to mammalian cells. During macrophage infection, the anti-cryptococcal effects of fenbendazole included inhibition of intracellular proliferation rates and reduced phagocytic escape through vomocytosis. Fenbendazole deeply affected the cryptococcal capsule. In a mice model of cryptococcosis, the efficacy of fenbendazole to control animal mortality was similar to that observed for amphotericin B. These results indicate that fenbendazole is a promising candidate for the future development of an efficient and affordable therapeutic tool to combat cryptococcosis.

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.

Seasonal and pandemic influenza causes 650,000 deaths annually in the world. The emergence of drug-resistance to specific anti-influenza drugs such as oseltamivir and baloxavir marboxil highlights the urgency of novel anti-influenza chemical entity discovery. In this study, we report a series of novel thiazolides derived from an FDA-approved drug nitazoxanide with antiviral activity against influenza and a broad range of viruses. The preferred candidates 4a and 4d showed significantly enhanced anti-influenza potentials with 10-fold improvement, compared with nitazoxanide, and were effective against a variety of influenza subtypes including oseltamivir-resistant strains. Notably, the combination using of compounds 4a/4d and oseltamivir carboxylate or zanamivir displayed synergistic antiviral effect against oseltamivir-resistant strain. Mode of action analysis demonstrated that compounds 4a/4d acted at the late phase of viral infection cycle through inhibiting viral RNA transcription and replication. Further experiments showed that treatment with compounds 4a/4d significantly inhibited influenza virus infection in human lung organoids, suggesting the druggability of the novel thiazolides. In-depth transcriptome analysis revealed a series of up-regulated cellular genes that may contribute to the antiviral activities of 4a/4d. Together, our study pointed the optimization direction of nitazoxanide as anti-influenza drug, and discovered two novel-structured candidates 4a/4d with relatively broad-spectrum antiviral potential.

Manogepix (APX001A) is the active moiety of the novel drug candidate fosmanogepix (APX001). We previously reported the broad-spectrum activity of manogepix but also observed a correlation between increased manogepix and fluconazole MICs. Here we extended this study and included isolates with acquired fluconazole resistance.

Isolates (n=835) were identified using CHROMagar, MALDI-TOF and, when needed, ITS-sequencing. EUCAST E.Def 7.3.1 susceptibility testing included manogepix, amphotericin B, anidulafungin, micafungin, fluconazole and voriconazole. Manogepix wildtype-upper-limit (WT-UL) values were established following EUCAST-principles for ECOFF setting allowing wildtype/non-wildtype classification. Drug-specific MIC correlations were investigated using Pearson's correlation.

Manogepix modal MICs were low (range 0.004-0.06 mg/L against 16/20 included species). Exceptions were C. krusei and C. inconspicua, and to a lesser extent C. kefyr and Pichia kluyveri. The activity was independent of Fks echinocandin hot-spot alterations (n=17). Adopting the WT-UL established for C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis and C. tropicalis, 14/724 (1.9%) isolates were non-wildtype for manogepix. Twelve of these (85.7%) were also non-wildtype for fluconazole. A statistically significant correlation was observed between manogepix and fluconazole MICs for C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis and C. tropicalis (Pearson r=0.401-0.575), but not between manogepix and micafungin or amphotericin B MICs for any species except C. tropicalis (r=0.519 for manogepix versus micafungin).

Broad-spectrum activity was confirmed for manogepix against contemporary yeast. However, a 1-4 two-fold-dilution increase in manogepix MICs is observed in a subset of isolates with acquired fluconazole resistance. Further studies on the potential underlying mechanism and implication for optimal dosing are warranted.

Ahead of Matchday 7, UEFA.com looks at some obvious selections and some lesser-owned options.

An educator's experience teaching math is important, but performance on math-content-certification tests is the best predictor of how well a teacher's students will perform in early algebra, finds a new study by the Regional Educational Laboratory Central at Marzano Research.

Zoom-bombings have been making headlines across the country this spring, and Penn State is no exception to the increase in security threats and breaches. To address these recent incidents in Zoom meetings, University-wide Zoom default setting changes will be implemented on May 11.

Verizon reportedly used Huawei technology in computer networking, download security, and video communications, with the Chinese company seeking compensation and royalties.

Group projects founder when students don't work well together. Here's the latest thinking on evaluating students on both content mastery and collaboration skills.

Ahead of Matchday 8, UEFA.com looks at some obvious #UCLfantasy selections and those who could cause a surprise.

The new 50-state report from the Rural School and Community Trust, emphasizes early childhood education and college-and-career readiness.

Researchers in Penn State’s College of Engineering, College of Agricultural Sciences and College of Medicine say direct LTP treatment and plasma-activated media are effective treatments against bacteria found in liquid cultures and have devised a way to create plasma directly in liquids.

Internal rate of return: remember that candidates must be sifted through the funnies sieve first.

The Sustainable Growth table offers it a most intriguing set of rankings to mull.

Attorney General Kathy Jennings today announced that she is joining a lawsuit opposing the Trump Administration’s new rule circumventing the Flores Settlement Agreement, which has governed the treatment of children in immigration custody since 1997. In the complaint before the U.S. District Court for the Central District of California, the coalition argues that the rule eliminates several critical protections […]