Being bullied can lead to adverse physical and mental health outcomes. Individuals who experience a sudden traumatic event often have short-term disturbances in their sleep patterns. Ongoing trauma may result in extended periods of sleep disruption.

Being bullied in elementary school predicts parasomnias, such as nightmares and night terrors, years later. General practitioners, pediatricians, parents, and teachers may consider parasomnias as potential signs of being bullied. (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)

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)

Early-life lower respiratory illnesses, including pneumonia, are associated with increased prevalence of asthma and diminished lung function in children. Whether early-life pneumonia is associated with subsequent impaired lung function and asthma in adults is not yet clear.

This is the first article providing strong data for an association between early-life pneumonia in an outpatient setting and airflow limitation and asthma into adulthood, supporting the hypothesis of the early-life origins of chronic obstructive pulmonary disease. (Read the full article)

Blood cultures are the most widely available diagnostic tool to identify bacterial pathogens in community-acquired pneumonia (CAP). Despite a recent national guideline recommendation for blood culture performance in children with moderate/severe CAP, there is still wide variation across institutions.

Using improvement methodology, we demonstrated that blood cultures can be routinely performed in children admitted for CAP, in accordance with a recent national guideline, without increasing length of stay in a setting with a low false-positive blood culture rate. (Read the full article)

Fifteen percent of tuberculosis cases globally are resistant to the drug isoniazid. Isoniazid resistance puts patients with tuberculosis at risk for poor treatment outcomes and threatens the effectiveness of isoniazid preventive therapy in people with latent tuberculosis infection.

We present the first global and regional estimates of the proportion of children with tuberculosis who have isoniazid-resistant disease, showing large geographic variations in risk of resistance. We estimate the number of annual incident cases of isoniazid-resistant tuberculosis in children. (Read the full article)

An increasing number of children are unvaccinated at entry into public schools, potentially endangering children who cannot be vaccinated for medical reasons and threatening herd immunity. Voluntary exemptions from immunizations vary geographically and by parental characteristics.

We find that exemption behavior is highest in peripheral areas of cities and that specific types of student populations are associated with high exemption rates. Additionally, there is spatial overlap between clusters of high personal exemption and medical exemption populations. (Read the full article)

The 2011 national guidelines for the management of pediatric community-acquired pneumonia recommended narrow-spectrum antibiotic therapy (eg, ampicillin) for most children hospitalized with pneumonia. Before the release of the guidelines, the use of broader-spectrum antibiotics (eg, third-generation cephalosporins) was much more common.

After release of the guidelines, third-generation cephalosporin use declined and penicillin/ampicillin use increased among children hospitalized with pneumonia. Changes were most apparent among institutions that proactively disseminated the guidelines, underscoring the importance of local efforts for timely guideline implementation. (Read the full article)

Weak recommendations exist to guide emergent neuroimaging decisions in children with first, unprovoked seizures. The prevalence of and risk factors associated with clinically relevant abnormalities on neuroimaging have not been well defined in prospective studies.

Clinically relevant intracranial abnormalities on neuroimaging occur in 11% of children with first, unprovoked seizures. Emergent/urgent abnormalities, however, occur in <1%, suggesting that most of these children do not require emergent neuroimaging. Specific clinical findings identify patients at higher risk. (Read the full article)

Stevens-Johnson syndrome (SJS) is a rare and severe immunologic phenomenon characterized by rash and mucous membrane disease. SJS may be triggered by medications and, less commonly, by infections such as Mycoplasma pneumoniae (Mp). Outbreaks of SJS are exceedingly rare.

We describe the largest SJS outbreak reported in children, which was also Mp-associated. In the first case-control study of this disease, we identify predictors of Mp-associated SJS versus non–Mp-associated SJS, including fewer skin lesions, pneumonia, and elevated erythrocyte sedimentation rate. (Read the full article)

Small-for-gestational-age neonates are at risk for thrombocytopenia during the first days and weeks after birth. However, the incidence, duration, severity, responsible mechanism, value of platelet transfusions, and risk of death from this variety of neonatal thrombocytopenia are unknown.

Ten percent of thrombocytopenic small-for-gestational-age neonates have a recognized cause for low platelets (aneuploidy, extracorporeal membrane oxygenation, disseminated intravascular coagulation); they have a high mortality rate (65%). Ninety percent have a moderate, transient (2 weeks), hyporegenerative thrombocytopenia with a low mortality rate (2%). (Read the full article)

Small for gestational age neonates (weight <10th percentile) are at risk for neutropenia during the first days after birth. However, the duration, responsible mechanism, and outcomes of this variety of neonatal neutropenia are not precisely known.

Six percent of small for gestational age neonates had neutrophils <1000/μL, with an average neutropenia duration of 7 days. Neutropenia was more closely linked with small for gestational age status than maternal hypertension. This neutropenia is associated with elevated nucleated red blood cell count and increased odds of necrotizing enterocolitis. (Read the full article)

For companies to survive and even thrive beyond the coronavirus pandemic, they’re going to have think more like the millennial generation, says Dr Anushka Bogdanov.

Flawed achievement-gap targets in the state's NCLB flexibility waiver force a do-over and highlight complexities.

Federal law requires states to report student test scores in achievement levels, but leaders in the Golden State want to take a different approach.

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.

Objectives: Carbapenemase-producing Enterobacterales and specifically KPC-producing Klebsiella pneumoniae (KPC-Kp) are rapidly spreading worldwide. The prognosis of ventilator-associated pneumonia (VAP) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) is not well known. Our study tries to assess whether ventilator-associated pneumonia caused by a KPC-Kp strain is associated with higher all-cause mortality than if caused by carbapenem-susceptible isolates.

Study design and methods: This is a retrospective cohort study of patients with VAP due to K. pneumoniae from a 35-bed polyvalent Intensive Care Unit in a university hospital (> 40,000 annual admissions) between January 2012 and December 2016. Adjusted multivariate analysis was used to study the association of KPC-Kp with 30-day all-cause mortality (Cox regression).

Results. We analyze 69 cases of K. pneumoniae VAP of which 39 were produced by a KPC-Kp strain with high-level resistance to meropenem (MIC > 16 mg/mL). All-cause mortality at 30 days was 41% in the KPC-Kp group (16/39) and 33.3% in the carbapenem-susceptible cases (10/30). KPC-Kp etiology was not associated with higher mortality when controlled for confounders (adjusted hazard ratio [lsqb]HR[rsqb] 1.25; 95% CI: 0.46–3.41). Adequate targeted therapy (HR 0.03; 95% CI: <0.01–0.23) was associated with all-cause mortality.

Conclussion. Assuming the limitations due to the available sample size, the prognosis of VAP caused by KPC-Kp is similar to VAPs caused by carbapenem-susceptible K. pneumoniae when appropriate treatment is used.

Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually for the last few years. Although studies on mechanisms of polymyxin are expanding, system-wide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapt to colistin (polymyxin E) pressure, we carried out proteomic analysis of Klebsiella pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in Klebsiella pneumoniae involving several pathways, including (i) gluconeogenesis and TCA cycle; (ii) arginine biosynthesis; (iii) porphyrin and chlorophyll metabolism; and (iv) enterobactin biosynthesis. Interestingly, decreased abundance of class A β-lactamases including TEM, SHV-11, SHV-4 were observed in cells treated with colistin. Moreover, we also present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant Klebsiella pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of Klebsiella pneumoniae ATCC BAA 2146, showed missense mutation in crrB. The crrB mutant Ci, which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose (L-Ara4N) and palmitoylation, showed striking increases of CrrAB, PmrAB, PhoPQ, ArnBCADT and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediate colistin resistance, which may further offer valuable information to manage polymyxin resistance.

Klebsiella pneumoniae that produce extended spectrum beta lactamases (ESBLs) are a persistent public health threat. There are relatively few therapeutic options and there is undue reliance on carbapenems. Alternative therapeutic options are urgently required. A combination of cefepime and the novel beta lactamase inhibitor enmetazobactam is being developed for treatment of serious infections caused by ESBL-producing organisms. The pharmacokinetics-pharmacodynamics (PK-PD) of cefepime-enmetazobactam against ESBL-producing K. pneumoniae was studied in a neutropenic murine pneumonia model. Dose ranging studies were performed. Dose fractionation studies were performed to define the relevant PD index for the inhibitor. The partitioning of cefepime and enmetazobactam into the lung was determined by comparing area under the concentration time curve (AUC) in plasma and epithelial lining fluid. The magnitude of drug exposure for cefepime-enmetazobactam required for logarithmic killing in the lung was defined using 3 ESBL-producing strains. Cefepime 100 mg/kg q8h i.v. had minimal antimicrobial effect. When this background regimen of cefepime was combined with enmetazobactam half-maximal effect was induced with enmetazobactam 4.71 mg/kg q8h i.v. The dose fractionation study suggest both fT>threshold and fAUC:MIC are potentially relevant PD indices. The AUC_ELF:AUC_plasma for cefepime and enmetazobactam was 73.4% and 61.5%, respectively. A ≥2-log kill in the lung was achieved with a plasma and ELF cefepime fT>MIC of ≥20% and enmetazobactam fT>2 mg/L of ≥20% of the dosing interval. These data and analyses provide the underpinning evidence for the combined use of cefepime and enmetazobactam for nosocomial pneumonia.

Treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP+Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) at 4-day intervals, plus allopurinol at 30 mg/kg/12 h p.o. during 130 days; LC+Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose), plus allopurinol during 130 days; Allop, treated with allopurinol only; non-treated control. Parasite loads were evaluated by quantitative PCR in liver, spleen and bone marrow and by immunohistochemistry in the ear skin, before, just after treatment and 4 months later. LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen and bone marrow 4 months after treatment, compared to the pre-treatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin, in comparison to the control group. On the basis of clinical staging and parasitological evaluations, LCP formulation exhibited a more favorable therapeutic profile, when compared to LC one, being therefore promising for treatment of canine visceral leishmaniasis.

Globally, mutations in the katG gene account for the majority of isoniazid-resistant strains of Mycobacterium tuberculosis. Buyankhishig et al analyzed a limited number of Mycobacterium tuberculosis strains in Mongolia and found that isoniazid resistance was mainly attributable to inhA mutations. The GenoType® MTBDRplus assay was performed for isolates collected in the First National Tuberculosis Prevalence Survey and the Third Anti-Tuberculosis Drug Resistance Survey to investigate genetic mutations associated with isoniazid resistance in Mycobacterium tuberculosis in Mongolia. Of the 409 isoniazid-resistant isolates detected by the GenoType® MTBDRplus assay, 127 (31.1%) were resistant to rifampicin, 294 (71.9%) had inhA mutations without katG mutations, 113 (27.6%) had katG mutations without inhA mutations, and two (0.5%) strains had mutations in both the inhA and katG genes. Of the 115 strains with any katG mutation, 114 (99.1%) had mutations in codon 315 (S315T). Of the 296 trains with any inhA mutation, 290 (98.0%) had a C–15T mutation. The proportion of isoniazid-resistant strains with katG mutations was 25.3% among new cases and 36.2% among retreatment cases (p=0.03), as well as 17.0% among rifampicin-susceptible strains and 52.8% among rifampicin-resistant strains (p<0.01). Rifampicin resistance was significantly associated with the katG mutation (adjusted odds ratio 5.36, 95% CI 3.3–8.67, p<0.001). Mutations in inhA predominated in isoniazid-resistant tuberculosis in Mongolia. However, the proportion of katG mutations in isolates from previously treated cases was higher than that among new cases, and that in cases with rifampicin resistance was higher than that in cases without rifampicin resistance.

Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem/vaborbactam in a KPC-3 producing K. pneumoniae isolate.

Peroxidases are a group of heterogeneous family of enzyme that plays diverse biological functions. Ascorbate peroxidase is a redox enzyme that is reduced by trypanothione, which plays a central role in the redox defence system of Leishmania. In view of developing new and novel therapeutics, we have performed in silico studies in order to search for ligand library and identification of new drug candidates and its physiological role against promastigotes and intracellular amastigotes of Leishmania donovani. Our results demonstrated that the selected inhibitor ZINC96021026 has significant anti-leishmanial effect and effectively killed both free and intracellular forms of the parasite. ZINC96021026 was found to be identical to ML-240, a selective inhibitor of Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family which was derived from the scaffold of DBeQ, targeting the D2-ATPase domain of the enzyme. ZINC96021026 (ML-240) thus have broad range of cellular functions, thought to be derived from its ability to unfold proteins or disassemble protein complexes besides inhibiting the ascorbate peroxidase activity. ML-240 may inhibits the parasite's ascorbate peroxidase leading to extensive apoptosis and inducing generation of reactive oxygen species. Taken together, our results demonstrated that ML-240 could be an attractive therapeutic option for treatment against leishmaniasis.

BACKGROUND AND OBJECTIVES:

Antibiotic therapy is often prescribed for suspected community-acquired pneumonia (CAP) in children despite a lack of knowledge of causative pathogen. Our objective in this study was to investigate the association between antibiotic prescription and treatment failure in children with suspected CAP who are discharged from the hospital emergency department (ED).

BACKGROUND:

Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly with a mortality of ~27%. The Congenital Diaphragmatic Hernia Study Group (CDHSG) developed a simple postnatal clinical prediction rule to predict mortality in newborns with CDH. Our aim for this study is to externally validate the CDHSG rule in the European population and to improve its prediction of mortality by adding prenatal variables.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

Matthew J. Lipshaw
Apr 1, 2020; 145:e20193138-e20193138
ARTICLES

France beat Croatia to earn a final tournament debut, as they joined Serbia, Romania and Poland in qualifying for UEFA Futsal EURO 2018 via the play-offs.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

That free Echo Dot will let you launch apps, search for titles, and switch inputs on your TV with just your voice.

Armenia's most famous footballing son, Henrikh Mkhitaryan is the U19 EURO ambassador and looks back at his own youth career.

Romania and Slovakia will stage the U19 EURO final tournaments in 2021 and 2022 respectively.

Chef and food writer Letitia Clark talks Ella Walker through her debut cookbook, Bitter Honey - an ode to the cooking of Sardinia.

Four Penn State World Campus energy and sustainability policy majors spent the year working with Pennsylvania boroughs to inventory greenhouse gas emissions, and coming up with climate action plans for reducing them.

Selected poems of Rachelle Bowser, Rachel Mennies, Erin Murphy and Eleanor Stanford have been chosen to represent the Pennsylvania Center for the Book’s 2020 Public Poetry Project, with poetry interpreted into art posters for the annual event.

Team news, coaches' views, form guide and key stats as Germany meet Romania.

• National team and staff raise money for health service

• Footballers use popularity to advise expats to stay away to safeguard health
• Bucharest’s two biggest clubs fund life-saving equipment for capital’s hospitals
• National stadium converted to 24/7 emergency helpline centre

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

Concern for their students and adapting to remote teaching are only a few of the stressors that teachers are facing during the coronavirus pandemic. In response, the Pennsylvania State Education Association (PSEA) has partnered with Sebrina Doyle, a graduate fellow in the College of Education, to offer mindfulness-based stress reduction training via Zoom to their members – to help alleviate feelings of helplessness, fear and anxiety. Doyle offered the hour-long webinar two days this month to approximately 700 PSEA members.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

Mathilde, a French teen, describes her trip to Bosnia-Herzegovina. She and others will raise funds for a youth centre where Bosnian teens can discover God.

California's budget reductions will result in some state curricular materials not reaching the state's schools until 2017 or later, Jack O'Connell says.

California's proposed curriculum guide in ethnic studies is being sent back for substantial revision after a pileup of criticism that it's anti-Semitic.

California, which has a mixed history when it comes to evidence-based reading instruction, has a plan to use federal funds for literacy programs that some say are out of sync with the science.

The lawsuit, filed in 2014, alleges that the state was severely underfunding schools, forcing school districts to lean heavily on property taxes, which especially disadvantages students in property-poor areas.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.

Slovenia's 1-0 first-leg defeat of Spain ended a string of streaks held by the European champions, including 27 straight wins and unbeaten runs of more than a decade.

Saskia perseveres through language learning and connects with a young Albanian girl who becomes a follower of Jesus.