THE Through the Keyhole Pandemic Special has certainly given rise to some entertaining sights.

Alan Gray – An Appreciation

For me, art galleries have always provided shelter from the storm. The tempest in question might be a literal one, such as Storm Dennis, who buffeted us all from on high last weekend, or it could simply be a sudden squall in the mind. Art in all forms can take us out of ourselves – even if it's for a split-second – and recalibrate the mind.

In California, nearly 1 in every 4 children don't speak English fluently. On Election Day, the state's voters will decide whether to overturn a longstanding policy of teaching these children in English-only classrooms, or whether to embrace bilingual forms of teaching.

A number of studies have examined the early impact of the varicella vaccination program on varicella-related hospitalizations and have found evidence of decline after vaccine implementation.

This study further documents the continued decline in varicella-related hospitalizations during the 1-dose varicella vaccination era and demonstrates statistically significant declines of >65% in all age groups. These data suggest that varicella vaccination prevented ~50 000 hospitalizations from 2000 to 2006. (Read the full article)

Nasal continuous positive airway pressure (NCPAP) has been the initial respiratory support for many preterm infants with respiratory distress syndrome (RDS). Nasal intermittent positive-pressure ventilation (NIPPV) seems to increase the beneficial effects of NCPAP by combining it with ventilatory inflations.

This study suggests that NIPPV, as an intial respiratory support for preterm infants with RDS, is feasible and safe and may have beneficial effects, when compared with NCPAP. (Read the full article)

Aluminum is ubiquitous and exposure is unavoidable. Adverse health effects have been associated with large exposures in workers or those with chronic kidney disease. There are no established age-specific reference ranges or toxicity data for populations of healthy children.

We demonstrate the wide variability of aluminum reference ranges in biological samples and that the ranges are not based on studies including healthy children. Further research is necessary to establish clinically relevant reference ranges for healthy children. (Read the full article)

The medical home is associated with beneficial outcomes in children with special health care needs and in the entire pediatric population. It is unknown if it benefits the majority of the pediatric population (ie, children without special health care needs).

This study is the first to demonstrate an association between the medical home and beneficial health care utilization, child health, and health-promoting behavior outcomes in children without special health care needs. (Read the full article)

High-grade vesicoureteral reflux is a risk factor for impaired renal function. Diagnosis by voiding cystourethrography is invasive and highly uncomfortable. As only a minority of children show high-grade vesicoureteral reflux, this exposes the majority to unnecessary distress.

This case-control study proved that high-grade vesicoureteral reflux is identifiable with high sensitivity using urinary proteome analysis, based on capillary electrophoresis coupled to mass spectrometry in a cohort suspected of having vesicoureteral reflux, thus sparing the majority of children from invasive diagnostics. (Read the full article)

Active video games can enable children under laboratory conditions to participate in moderate, and even vigorous, physical activity. There are inconsistencies in the literature, however, about whether active video games enable children to increase physical activity under more naturalistic circumstances.

This study tests whether children receiving a new active video game spontaneously engaged in more physical activity, and whether commercially available active video games have a public health benefit. No additional physical activity was detected, suggesting no public health benefit. (Read the full article)

Dimenhydrinate, an antihistaminic agent, is a widely used drug in Canada and Europe. It limits stimulation of the vomiting center via the vestibular system. Multiple studies have shown its effectiveness in the treatment of vertigo and postoperative nausea and vomiting.

Dimenhydrinate, when given orally, did not significantly decrease the frequency of vomiting in children with acute gastroenteritis compared with placebo. The reported adverse effect proportions were similar for the dimenhydrinate and placebo groups. (Read the full article)

Percentile charts for birth weight are used to assess the somatic development of neonates (small, appropriate, or large for gestational age).

A systematic error was identified in the majority of birth weight percentile charts. As a consequence, small for gestational age rates are overestimated and large for gestational age rates are underestimated; ~5% of neonates are misclassified. (Read the full article)

Cholestasis predisposes to the development of fat-soluble vitamin (FSV) deficiency. D-α tocopheryl polyethylene glycol-1000 succinate and coadministered FSVs are absorbed in spite of cholestasis.

Infants with biliary atresia with total bilirubin >2 mg/dL are at risk for fat-soluble vitamin (FSV) deficiency. A multivitamin preparation containing d-α tocopheryl polyethylene glycol-1000 succinate alone is not effective in treating biochemical FSV insufficiency in cholestatic infants. (Read the full article)

Adolescents living in lower-poverty neighborhoods have better mental health than youth in high-poverty contexts, but it is unclear if associations are causal. Furthermore, it is unknown why some youth benefit more than others from moving to more advantaged neighborhoods.

Using an experimental study that randomly assigned families to receive vouchers to move to lower-poverty neighborhoods, we found that recent violent crime victimization adversely modified the mental health effects of moving to better neighborhoods. (Read the full article)

Most term and late preterm infants with neonatal encephalopathy have not had recognized asphyxial birth events. Several nonasphyxial risk factors for neonatal encephalopathy have been identified in previous studies.

In a large sample, we confirm the association of several nonasphyxial factors with neonatal encephalopathy, including markers of intrauterine exposure to infection or inflammation, intrauterine fetal growth restriction, and birth defects. We identify steps that would improve studies of neonatal encephalopathy. (Read the full article)

Although a number of cross-sectional studies have documented associations between teen dating violence victimization and adverse health outcomes, including sexual risk behaviors, suicidality, substance use, and depression, longitudinal work examining the relationship between victimization and outcomes is limited.

This study is the first to demonstrate the longitudinal associations between teen dating violence victimization and multiple young adult health outcomes in a nationally representative sample. Findings emphasize the need for screening and intervention for both male and female victims. (Read the full article)

Part C early intervention serves ~2.8% of US children who are younger than 3 years old; however, there is evidence that substantial numbers of infants and toddlers with developmental delays receive no early intervention services.

Broad eligibility criteria can classify children who have no delays or minimal delays as candidates for Part C services. Despite this, no jurisdiction provides Part C services to all children who have substantial delays. (Read the full article)

Pneumococcal conjugate vaccines are effective in preventing pneumococcal disease but are also costly. Although the current US immunization schedule recommends 4 doses, many countries have adopted 3-dose schedules that have worked well, but may provide less protection against pneumococcal disease.

Changing the US 13-valent pneumococcal conjugate vaccine schedule from 3 to 2 primary doses while keeping a booster dose would save $412 million annually but might lead to moderate increases in pneumococcal disease, especially otitis media and pneumonia. (Read the full article)

Respiratory outcomes of patients with bronchopulmonary dysplasia (BPD) range from no oxygen requirement to chronic respiratory failure. Outcomes of least severe types of BPD are well described. Limited data exist on outcomes of patients with BPD-related chronic ventilator dependency.

Along with a first estimation of the incidence of patients with severe BPD-related chronic respiratory failure who were dependent on positive pressure ventilation via tracheostomy at home, we describe their survival rate, liberation from positive pressure ventilation, and decannulation. (Read the full article)

The 1-dose childhood varicella vaccination program in the United States resulted in dramatic declines in varicella incidence, hospitalizations, and deaths. There is little information on the impact of the 2006 recommendation for 2-dose varicella vaccination of children on varicella epidemiology.

In the first 5 years of the 2-dose varicella vaccination program, declines in varicella incidence were seen in all age groups, including infants who are not eligible for varicella vaccination, providing evidence of the benefit of high population immunity. (Read the full article)

Cooling infants with hypoxic-ischemic encephalopathy shortly after birth improves survival and neurodevelopmental outcome. The optimal way to cool infants during transfer to regional NICUs is unclear.

Data from a regional neonatal transfer team, using first passive and subsequently active cooling for these infants, suggest that active cooling results in improved thermal control and a reduction in stabilization time. (Read the full article)

Sibship size has been negatively associated with children’s language, cognitive, and academic outcomes. This phenomenon is often explained in terms of resource dilution, wherein more children in the home is associated with fewer parental resources allocated to each child.

The current study identifies a moderator of this relationship. Specifically, if children’s next-in-age older siblings exhibit high levels of cognitive sensitivity then sibship size is not significantly related to children’s vocabulary. (Read the full article)

Individuals with DiGeorge syndrome (DGS) have varying degrees of immunodeficiency. All are susceptible to vaccine-preventable infections with serious complications. Although live vaccines are generally contraindicated in this population, limited evidence suggests that they may be effective and safe for select individuals.

Many individuals with DGS received live vaccines despite having a known diagnosis. Adverse events following live immunizations were typically minor and self-limited, suggesting that live vaccines may be considered for patients with DGS who exhibit mild-to-moderate immunosuppression. (Read the full article)

Invasive pneumococcal disease causes enormous morbidity in children. The spectrum and severity of illness caused by pneumococcal serotypes not present in the current vaccine, and whether the clinical profile and severity of disease have changed, are largely unknown.

Initial data suggest that nonvaccine serotypes are more common in children with underlying conditions, who have greater morbidity from disease. In the post-PCV13 era, a larger proportion of patients are hospitalized, but mortality rates are unchanged. (Read the full article)

A substantial gap exists between what is recommended for effective primary care of children and what takes place. Patient-centered health information technologies have been used to gather information and counsel parents, however, have not been integrated directly with electronic health records nor been speech-based to improve decision-making at the point-of-care.

This study shows that a ubiquitous technology, the telephone, can be successfully used to automatically assess and counsel parents before pediatric primary care visits as well as inform their primary care clinicians in a way that is feasible and effective for multiple important issues. (Read the full article)

The World Health Organization recommends using vaccination contacts to deliver high-dose vitamin A supplementation (VAS) to children aged 6 to 59 months. The effect of this policy on overall child mortality has not been assessed.

In this first randomized controlled trial of VAS at routine vaccination contacts after 6 months, VAS had no overall effect on mortality but was associated with reduced mortality in girls and increased mortality in boys. (Read the full article)

Lung ultrasound outperforms conventional radiology in the emergency diagnosis of pneumothorax and pleural effusions. In the pediatric age, lung ultrasound has been also successfully applied to the fluid-to-air transition after birth and to rapid pneumonia diagnosis.

Nasal ventilation has dramatically decreased the need for invasive mechanical respiratory support. This study demonstrates that, after a short trial on nasal continuous positive airway pressure, lung ultrasonography reliably predicts the failure of noninvasive ventilation unlike the conventional chest radiogram. (Read the full article)

Infants who require positive pressure ventilation at birth are considered to be at risk for subsequent compromise and are recommended to receive postresuscitation care. The supportive evidence and details of this care have not been fully investigated.

We investigate the need for postresuscitation care in infants who require positive pressure ventilation at birth, review the aspects of care needed, and explore the important risk factors most predictive of it. (Read the full article)

There are discrepancies regarding which treatment is best in clinical practice for children with parapneumonic empyema, with some authors favoring video-assisted thoracoscopy and others favoring intrapleural fibrinolytic agents.

This study is one of the few randomized clinical trials on this subject in children and the first multicenter trial. It exclusively included patients with septated empyema. Thoracoscopy and fibrinolysis with urokinase were equally effective for this condition. (Read the full article)

Pneumococcal conjugated vaccines (PCVs) are known to decrease invasive pneumococcal disease in children, but their effect on pneumonia necessitating hospitalization is more variable across study sites, and effects on hospitalization for sinusitis have not been shown previously.

There was a significant decrease in hospitalizations for sinusitis in children <2 years of age, and hospitalization for pneumonia decreased in children aged <5 years after sequential introduction of PCV7 and PCV13. (Read the full article)

Although pediatric professional guidelines emphasize addressing a child’s social environment in the context of well child care, it remains unclear whether screening for unmet basic needs at visits increases low-income families’ receipt of community-based resources.

This study demonstrates that systematically screening and referring for social determinants of health during primary care can lead to the receipt of more community resources for families. (Read the full article)

Increased central adrenergic activity occurs with opiate withdrawal. Clonidine is an effective drug as an adjunct to morphine in the treatment of neonatal abstinence syndrome. It is unclear whether clonidine is effective as single-drug therapy.

Clonidine, a α₂-adrenergic agonist, seems to be as effective as morphine when used as a single-drug therapy for neonatal abstinence syndrome. Its administration results in improvement in neurobehavioral performance. (Read the full article)

Noninvasive ventilation (NIV) reduced the need of intubation in preterm infants with RDS. However, randomized studies comparing nasal synchronized intermittent positive pressure ventilation and bilevel continuous positive airway pressure are still lacking.

The present study shows no differences in short-term outcomes between 2 different NIV strategies, nasal synchronized intermittent positive pressure ventilation and bilevel continuous positive airway pressure, in preterm infants for the initial treatment of RDS. (Read the full article)

Preterm infants are at an increased risk of infections; therefore, vaccination is of particular importance. Because immune response data reported for preterm infants may vary according to gestational age and vaccination timing, vaccine responses in this population warrant additional research.

This study evaluated 13-valent pneumococcal conjugate vaccine in preterm infants. Results suggest that this vaccine was well tolerated and immunogenic; most subjects achieved serotype-specific immunoglobulin G antibody levels and functional antibody responses likely to correlate with protection against invasive disease. (Read the full article)

Firearms are among the 10 leading causes of injury-related death for youth and continues throughout the life span. Annually youth homicides and assault-related injuries result in an estimated $16 million in combined medical and work loss costs.

Findings add to the field’s broadening conceptualization of youth victimization highlighting the potentially highly consequential risk factor of firearm and other weapon exposure as a component of victimization experiences on the mental health of youth. (Read the full article)

Conventional invasive pneumococcal disease (IPD) definition using laboratory confirmation lacks sensitivity. Using a vaccine-probe design, the FinIP trial showed that IPD disease burden and vaccine-preventable disease incidence were fourfold higher when a more sensitive outcome, clinically suspected IPD, was used.

Vaccine-preventable disease incidence (ie, absolute reduction due to PCV10 vaccination) during routine vaccination program was threefold with the more sensitive outcome of clinically suspected IPD compared with the conventional IPD definition. This has major implications for cost-effectiveness of PCVs. (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.

The issue is significant not only for school employment but also for whether a related federal law would protect students on the same basis.

A training session designed to improve players' ability in one-on-one and two-on-two situations.

Contezolid (MRX-I), a new oxazolidinone, is an antibiotic in development for treating complicated skin and soft tissue infections (cSSTI) caused by resistant Gram-positive bacteria. This was a thorough QT study conducted in 52 healthy subjects who were administered oral contezolid at a therapeutic (800 mg) dose, a supratherapeutic (1600 mg) dose, placebo, and oral moxifloxacin 400 mg in 4 separate treatment periods. The pharmacokinetic profile of contezolid was also evaluated. Time-point analysis indicated that the upper bounds of the two-sided 90% confidence interval (CI) for placebo-corrected change-from-baseline QTc (QTc) were <10 ms for the contezolid therapeutic dose at each time point. The upper bound of the 90% CI for QTc were slightly more than 10 ms with the contezolid supratherapeutic dose at 3 and 4 hours postdose, and the prolongation effect on the QT/QTc interval was less than that of the positive control, moxifloxacin 400 mg. At 3 and 4 h after the moxifloxacin dose, the moxifloxacin group met the assay sensitivity criteria outlined in ICH Guidance E14 with having a lower confidence bound ≥5 ms. The results of a linear exposure-response model which were similar to that of a time point analysis demonstrated a slightly positive relationship between contezolid plasma levels and QTcF interval with a slope of 0.227 ms per mg/L (90% CI: 0.188 to 0.266). In summary, contezolid did not prolong the QT interval at a therapeutic dose and may have a slight effect on QT interval prolongation at a supratherapeutic dose.

Bunyaviruses are significant human pathogens, causing diseases ranging from hemorrhagic fevers to encephalitis. Among these viruses, La Crosse virus (LACV), a member of the California serogroup, circulates in the eastern and midwestern United States. While LACV infection is often asymptomatic, dozens of cases of encephalitis are reported yearly. Unfortunately, no antivirals have been approved to treat LACV infection. Here, we developed a method to rapidly test potential antivirals against LACV infection. From this screen, we identified several potential antiviral molecules, including known antivirals. Additionally, we identified many novel antivirals that exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a known determinant of LACV entry. We extended these results to other ionophores and found that the antiviral activity of valinomycin extended to other viral families including bunyaviruses (Rift Valley fever virus, Keystone virus), enteroviruses (Coxsackievirus, rhinovirus), flavirivuses (Zika), and coronaviruses (HCoV-229E and MERS-CoV). In all viral infections, we observed significant reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of potassium ions to virus infection, suggesting a potential therapeutic target to disrupt virus replication.

Importance No antivirals are approved for the treatment of bunyavirus infection. The ability to rapidly screen compounds and identify novel antivirals is one means to accelerate drug discovery for viruses with no approved treatments. We used this approach to screen hundreds of compounds against La Crosse virus, an emerging bunyavirus that causes significant disease, including encephalitis. We identified several known and previously unidentified antivirals. We focused on a potassium ionophore, valinomycin, due to its promising in vitro antiviral activity. We demonstrate that valinomycin, as well as a selection of other ionophores, exhibits activity against La Crosse virus as well as several other distantly related bunyaviruses. We finally observe that valinomycin has activity against a wide array of human viral pathogens, suggesting that disrupting potassium ion homeostasis with valinomycin may be a potent host pathway to target to quell virus infection.

Despite the worldwide re-emergence of the chikungunya virus (CHIKV) and the high morbidity associated with CHIKV infections, there is no approved vaccine or antiviral treatment available. We here aim to identify the target of a novel class of CHIKV inhibitors i.e. CHVB series. CHVB compounds inhibit the in vitro replication of CHIKV isolates with 50% effective concentrations in the low micromolar range. A CHVB-resistant variant (CHVB^res) was selected that carried two mutations in the gene encoding nsP1 (responsible for viral RNA capping), one mutation in nsP2 and one mutation in nsP3. Reverse genetics studies demonstrated that both nsP1 mutations were necessary and sufficient to achieve ~18-fold resistance, suggesting that CHVB targets viral mRNA capping. Interestingly, CHVB^res was cross-resistant to the previously described CHIKV capping inhibitors from the MADTP series, suggesting they share a similar mechanism of action. In enzymatic assays, CHVB inhibited the methyltransferase and guanylyltransferase activities of alphavirus nsP1 proteins. To conclude, we identified a class of CHIKV inhibitors that targets the viral capping machinery. The potent anti-CHIKV activity makes this chemical scaffold a potential candidate for CHIKV drug development.

Ebola Virus (EBOV) is among the most devastating pathogens causing fatal hemorrhagic fever in humans. The 2013–2016 epidemics resulted in over 11000 deaths, while another outbreak is currently ongoing. Since there is no FDA-approved drug so far to fight EBOV infection, there is an urgent need to focus on drug discovery. Considering the tight correlation between the high EBOV virulence and its ability to suppress the type-I Interferon (IFN-I) system, identifying molecules targeting viral protein VP24, one of the main virulence determinants blocking IFN response, is a promising novel anti-EBOV therapy approach. Hence, in the effort of finding novel EBOV inhibitors, a screening of a small set of flavonoids was performed, showing that Quercetin and Wogonin can suppress the VP24 effect on IFN-I signaling inhibition. The mechanism of action of the most active compound, Quercetin, showing an IC₅₀ value of 7.4 μM, was characterized to significantly restore the IFN-I signaling cascade, blocked by VP24, by directly interfering with the VP24 binding to karyopherin-α and thus restoring P-STAT1 nuclear transport and IFN genes transcription. Quercetin significantly blocked viral infection, specifically targeting EBOV VP24 anti-IFN-I function. Overall, Quercetin is the first identified inhibitor of the EBOV VP24 anti-IFN function, representing a molecule interacting with a viral binding site that is very promising for further drug development aiming to block EBOV infection at the early steps.

The surge in stocks was on the back of positive news from trials being conducted on a potential treatment for the coronavirus. With most economies looking to partially reopen their economies, this brought a jump across most asset classes including commodities.

Sabric, a financial crime information centre, shares its tips on staying safe over the festive season.

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