Comparison of seven heterophile antibody assays for laboratory diagnosis of infectious mononucleosis in pediatric patients.

Heterophile antibody assays have been used to aid the diagnosis of infectious mononucleosis caused by the Epstein-Barr virus. Seven commercially available assays currently widely utilized in clinical laboratories were compared in this study. Variable performance characteristics and assay times are observed, and these pieces of data may assist clinical laboratories in assay selection and result interpretation.

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs.

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years) were compared. The median adjusted Ct value for asymptomatic children was 10.3 cycles higher than for symptomatic children (P < 0.0001), and VL were 3 to 4 logs lower than for symptomatic children (P < 0.0001); differences were consistent (P < 0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (odds ratio [OR], 6.5; P = 0.01), a recent contact (OR, 2.3; P = 0.02), and testing for surveillance (OR, 2.7; P = 0.005) had higher estimated risks of having a Ct value in the lowest quartile than children without, while an immunocompromised status had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in their nasopharynx/oropharynx than symptomatic children, but the timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

Evaluation of Commercial Molecular Diagnostic Methods for Detection and Determination of Macrolide Resistance in Mycoplasma pneumoniae.

We evaluated six commercial molecular tests targeting Mycoplasma pneumoniae, namely, the BioFire FilmArray respiratory panel (RP), the Meridian Alethia Mycoplasma Direct, the GenMark ePlex respiratory pathogen panel (RPP), the Luminex NxTAG RPP, the ELITech ELITe InGenius Mycoplasma MGB research use only (RUO) PCR, and the SpeeDx Resistance Plus MP assays. Laboratory-developed PCR assays at the University of Alabama at Birmingham and the Centers for Disease Control and Prevention were used as reference standards. Among 428 specimens, 212 were designated confirmed positives for M. pneumoniae The highest clinical sensitivities were found with the InGenius PCR (99.5%) and the FilmArray RP (98.1%). The Resistance Plus MP identified 93.3% of the confirmed-positive specimens, whereas 83.6, 64.6, and 55.7% were identified by the ePlex RPP, NxTAG RPP, and Mycoplasma Direct assays, respectively. There was no significant difference between the sensitivity of the reference methods and that of the FilmArray RP and InGenius assays, but the remaining four assays detected significantly fewer positive specimens (P < 0.05). Specificities of all assays were 99.5 to 100%. The Resistance Plus MP assay detected macrolide resistance in 27/33 specimens, resulting in a sensitivity of 81.8%. This study provides the first large-scale comparison of commercial molecular assays for detection of M. pneumoniae in the United States and identified clear differences among their performance. Additional studies are necessary to explore the impact of various test performances on patient outcome.

Laboratory Diagnosis of Neonatal Herpes Simplex Virus Infections.

Herpes simplex virus (HSV) is a common and often benign infection in humans; although it less commonly affects newborns, infection in this age group can be devastating. Newborns often present with nonspecific clinical findings, making timely and accurate diagnosis of infection critical. A wide variety of tests are available for detecting herpes simplex virus infection, but only a subset are useful and validated in the newborn population. The current review summarizes available diagnostic testing for neonatal disease, including discussing limitations, unmet needs, and emerging data on molecular testing methods.

Analysis of ß-Lactamase Resistance Determinants in Enterobacteriaceae from Chicago Children: a Multicenter Survey.

Multidrug-resistant (MDR) Enterobacteriaceae infections are increasing in U.S. children; however, there is a paucity of multicentered analyses of antibiotic resistance genes responsible for MDR phenotypes among pediatric Enterobacteriaceae isolates. In this study, 225 isolates phenotypically identified as extended-spectrum ß-lactamase (ESBL) or carbapenemase producers, recovered from children ages 0 to 18 years hospitalized between January 2011 and April 2015 at three Chicago area hospitals, were analyzed. We used DNA microarray platforms to detect ESBL, plasmid-mediated AmpC (pAmpC), and carbapenemase type ß-lactamase (bla) genes. Repetitive-sequence-based PCR and multilocus sequence typing (MLST) were performed to assess isolate similarity. Plasmid replicon typing was conducted to classify plasmids. The median patient age was 4.2 years, 56% were female, and 44% presented in the outpatient setting. The majority (60.9%) of isolates were Escherichia coli and from urinary sources (69.8%). Of 225 isolates exhibiting ESBL- or carbapenemase-producing phenotypes, 90.7% contained a bla gene. The most common genotype was the blaCTX-M-1 group (49.8%); 1.8% were carbapenem-resistant Enterobacteriaceae (three blaKPC and one blaIMP). Overall, pAmpC (blaACT/MIR and blaCMY) were present in 14.2%. The predominant E. coli phylogenetic group was the virulent B2 group (67.6%) associated with ST43/ST131 (Pasteur/Achtman MLST scheme) containing the blaCTX-M-1 group (84%), and plasmid replicon types FIA, FII, and FIB. K. pneumoniae harboring blaKPC were non-ST258 with replicon types I1 and A/C. Enterobacter spp. carrying blaACT/MIR contained plasmid replicon FIIA. We found that ß-lactam resistance in children is diverse and that certain resistance mechanisms differ from known circulating genotypes in adults in an endemic area. The potential impact of complex molecular types and the silent dissemination of MDR Enterobacteriaceae in a vulnerable population needs to be studied further.

Comparison of illumigene Group A Streptococcus Assay with Culture of Throat Swabs from Children with Sore Throats in the New Zealand School-Based Rheumatic Fever Prevention Program.

Group A streptococcal (GAS) pharyngitis is a particularly important condition in areas of New Zealand where the incidence of acute rheumatic fever remains unacceptably high. Prompt diagnosis and treatment of GAS pharyngitis are cornerstones of the Rheumatic Fever Prevention Programme, but these are hindered by the turnaround time of culture. Tests with excellent performance and rapid turnaround times are needed. For this study, throat swabs (Copan ESwabs) were collected from schoolchildren self-identifying with a sore throat. Samples were tested by routine culture and the illumigene GAS assay using loop-mediated isothermal amplification. Discrepant results were resolved by retesting of the same specimen by an alternative molecular assay. Seven hundred fifty-seven throat swab specimens were tested by both methods. The performance characteristics of the illumigene assay using culture on blood agar as the "gold standard" and following discrepancy analysis were as follows: sensitivity, 82% and 87%, respectively; specificity, 93% and 98%, respectively; positive predictive value, 61% and 88%, respectively; and negative predictive value, 97% and 97%, respectively. In our unique setting of a school-based throat swabbing program, the illumigene assay did not perform quite as well as described in previous reports. Despite this, its improved sensitivity and rapid turnaround time compared with those of culture are appealing.

Macrolide-Resistant Mycoplasma pneumoniae, United States.

Macrolide-resistant Mycoplasma pneumoniae (MRMP) is highly prevalent in Asia and is now being reported from Europe. Few data on MRMP are available in the United States. Using genotypic and phenotypic methods, we detected high-level MRMP in 13.2% of 91 M. pneumoniae--positive specimens from 6 US locations.

Comparison of Molecular Characteristics of Mycoplasma pneumoniae Specimens Collected from the United States and China.

Mycoplasma pneumoniae-positive clinical specimens obtained from the United States and China during the same period were studied for their molecular characteristics. We found much more diverse genotypes and a lower prevalence of macrolide resistance in the U.S. specimens. Data from the study also showed an association of the resistance with certain genotypes.

Rapid identification of pathogens from pediatric blood cultures by use of the FilmArray blood culture identification panel.

The performance of the FilmArray blood culture identification (BCID) panel has been studied in adult patients. We describe here an evaluation of this assay for the rapid identification of pathogens in Bactec Peds Plus/F and Bactec standard anaerobic/F bottles that contained blood samples from pediatric patients at a tertiary care children's hospital.

Trichosporon mycotoxinivorans infection in patients with cystic fibrosis.

We describe the clinical course of four patients who had Trichosporon mycotoxinivorans recovered from multiple sputum cultures over time with various clinical consequences but no fatalities. We also report successful rapid identification of this organism using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry.

Curcumin-loaded keratin-chitosan hydrogels for enhanced peripheral nerve regeneration.

Peripheral nerve injury often leads to symptoms of motor and sensory impairment, and slow recovery of nerves after injury and limited treatment methods will aggravate symptoms or even lead to lifelong disability. Curcumin can promote peripheral nerve regeneration, but how to accurately deliver the appropriate concentration of curcumin in the local peripheral nerve remains to be solved. In this study, we designed a human hair keratin/chitosan (C/K) hydrogel with sodium tripolyphosphate ions crosslinked to deliver curcumin topically. Chitosan improves the mechanical properties of hydrogels and keratin improves the biocompatibility of hydrogels. C/K hydrogel showed good cytocompatibility, histocompatibility and degradability. In vitro experiments showed that hydrogels can continuously release curcumin for up to 10 days. In addition, a comprehensive analysis of behavioral, electrophysiological, histology, and target organ recovery results in animal experiments showed that locally delivered curcumin can enhance nerve regeneration in addition to hydrogels. In short, we provide a new method that combines the advantages of human hair keratin, chitosan, and curcumin for nerve damage repair.

Recent developments in wearable piezoelectric energy harvesters.

Wearable piezoelectric energy harvesters (WPEHs) have gained popularity and made significant development in recent decades. The harvester is logically built by the movement patterns of various portions of the human body to harvest the movement energy and immediately convert it into usable electrical energy. To directly power different microelectronic devices on the human body, a self-powered device that does not require an additional power supply is being created. This Review provides an in-depth review of WPEHs, explaining the fundamental concepts of piezoelectric technology and the materials employed in numerous widely used piezoelectric components. The harvesters are classed according to the movement characteristics of several portions of a person's body, such as pulses, joints, skin, and shoes (feet). Each technique is introduced, followed by extensive analysis. Some harvesters are compared, and the benefits and drawbacks of each technique are discussed. Finally, this Review presents future goals and objectives for WPEH improvement, and it will aid researchers in understanding WPEH to the point of more efficient wireless energy delivery to wearable electronic components.

Detection of Streptococcus pyogenes by use of Illumigene group A Streptococcus assay.

The performance of the Illumigene group A Streptococcus assay was evaluated by comparing it to culture using 437 consecutive throat swabs. The Illumigene assay was also directly compared to PCR with 161 samples. This Illumigene assay is rapid and easy to perform. The assay also has high sensitivity (100%) compared to culture or PCR and high specificity (99.2%) compared to PCR. A total of 8.8% of the isolates were erythromycin resistant, and 6.9% were clindamycin resistant.

The impact of infection control upon hospital-acquired influenza and respiratory syncytial virus.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza are important pediatric community-acquired (CA) and hospital-acquired (HA) pathogens. The occurrence of pandemic (H1N1) 2009 influenza resulted in additional efforts to intensify infection control (IC) strategies. We detail the impact of IC strategies between 2003 and 2010 on influenza and RSV. METHODS: We assessed the rates of CA infections per 100 admissions and HA infections per 1000 patient-days for both RSV and influenza at Children's Memorial Hospital during the winter seasons (September through May) 2003-2010. The season of 2009, however, was extended through June due to ongoing admissions as a result of pandemic (H1N1) 2009 influenza. IC strategies implemented in response to pandemic (H1N1) 2009 influenza are described. The transmission ratio (HA cases/CA cases) was determined and correlated with IC efforts. RESULTS: Substantial season- to-season variability exists for CA RSV and CA influenza rates. The rates of HA RSV and HA influenza and the transmission ratios for these viruses remained unchanged in 2009-10 in comparison to the prior year (at 0.02 and 0.01, respectively) despite implementation of multiple IC strategies. In contrast, since 2005 an inverse association was noted between hand hygiene compliance and the transmission ratio of both RSV and influenza, with Spearman correlation coefficients of -0.84 (p = 0.051) and -0.89 (p = 0.008), respectively. CONCLUSIONS: We observed that improvements in hand hygiene compliance correlated with less transmission of RSV and influenza in the hospital. The important role of hand hygiene in preventing transmission of RSV and influenza to hospitalized children should be emphasized.

Single-cell RNA datasets and bulk RNA datasets analysis demonstrated C1Q+ tumor-associated macrophage as a major and antitumor immune cell population in osteosarcoma.

Background: Osteosarcoma is the most frequent primary bone tumor with a poor prognosis. Immune infiltration proved to have a strong impact on prognosis. We analyzed single-cell datasets and bulk datasets to confirm the main immune cell populations and their properties in osteosarcoma. Methods: The examples in bulk datasets GSE21257 and GSE32981 from the Gene Expression Omnibus database were divided into two immune infiltration level groups, and 34 differentially expressed genes were spotted. Then, we located these genes among nine major cell clusters and their subclusters identified from 99,668 individual cells in single-cell dataset GSE152048 including 11 osteosarcoma patients. Especially, the markers of all kinds of myeloid cells identified in single-cell dataset GSE152048 were set to gene ontology enrichment. We clustered the osteosarcoma samples in the TARGET-OS from the Therapeutically Applicable Research to Generate Effective Treatments dataset into two groups by complete component 1q positive macrophage markers and compared their survival. Results: Compared with the low-immune infiltrated group, the high-immune infiltrated group showed a better prognosis. Almost all the 34 differentially expressed genes expressed higher or exclusively among myeloid cells. A group of complete component 1q-positive macrophages was identified from the myeloid cells. In the bulk dataset TARGET-OS, these markers and the infiltration of complete component 1q-positive macrophages related to longer survival. Conclusions: Complete component 1q-positive tumor-associated macrophages were the major immune cell population in osteosarcoma, which contributed to a better prognosis.

Research on a rotary piezoelectric wind energy harvester with bilateral excitation.

This paper describes a rotary piezoelectric wind energy harvester with bilateral excitation (B-RPWEH) that improves power generation performance. The power generating unit in the current piezoelectric cantilever wind energy harvester was primarily subjected to a periodic force in a single direction. The B-RPWEH adopted a reasonable bilateral magnet arrangement, thus avoiding the drawbacks of limited piezoelectric cantilever beam deformation and unstable power generation due to unidirectional excitation force. The factors affecting the power generation were theoretically analyzed, and the natural frequency and excitation force of the piezoelectric cantilever have been simulated and analyzed. A comprehensive experimental research method was used to investigate the output performance. The B-RPWEH reaches a maximum output voltage of 20.48 Vpp when the piezoelectric sheet is fixed at an angle of 30°, the Savonius turbine number is 3, and the magnet diameter is 8 mm. By adjusting the fixed angle of the piezoelectric sheet, the number of Savonius wind turbine blades, and the magnet diameter, the maximum voltage is increased by 52.38%, 4.49%, and 245.95%, respectively. The output power is 24.5 mW with an external resistor of 8 kΩ, and the normalized power density is 153.14 × 10-3 mW/mm3, capable of powering light-emitting diodes (LEDs). This structure can drive wireless networks or low-power electronics.

Design and research of piezoelectric energy harvesting device applicable to wireless mouse.

This paper presents a piezoelectric energy harvesting device applicable to wireless mouse (WM-PEH). Adding magnetic force to the excitation piezoelectric generating unit makes the impact better and more pronounced. The polygonal roller can increase the excitation frequency of the piezoelectric generating unit and broaden the energy collection range and capability of the WM-PEH. The theoretical and simulation analysis of WM-PEH was carried out in this paper. The effects of the length ratio of the exciter rod to the support frame and the circular impact area on the output characteristics of the prototype were discussed in the experiment. When the length ratio of the exciter rod and the support rod is 3:1, the activity increment of the exciter rod is the largest, and the maximum output voltage can reach 42 V and the maximum output power is 22.43 mW when it acts on a circular generator set with a radius of 1.5 mm. The design of the device is highly integrated with the wireless mouse that is widely used, and the piezoelectric energy harvesting mechanism and the wireless mouse are perfectly combined, which provides a scientific basis for the subsequent development of a self-powered wireless mouse.

Renal-friendly Li+-doped carbonized polymer dots activate Schwann cell autophagy for promoting peripheral nerve regeneration.

Activation of autophagy in Schwann cells (SCs) has emerged as a powerful trigger for peripheral nerve injury (PNI) repair. Lithium ion (Li+) is a classical autophagy activator that plays an important role in promoting axonal extension and remyelination. However, the therapeutic window of existing lithium drugs is extremely narrow, and the adverse side effects, especially nephrotoxicity, severely limit their therapeutic value. Herein, Li+-doped carbonized polymer dots (Li-CPDs) was synthesized for the first time to change the pharmacokinetics of Li+ from occupying epithelial sodium channels to lipid raft-mediated endocytosis. The in-vivo results confirmed that Li-CPDs could accelerate the removal of myelin debris and promote nerve regeneration via activating autophagy of SCs. Moreover, Li-CPDs exhibited almost no renal toxicity compared to that of raw lithium drugs. Thus, Li-CPDs could serve as a promising Li+-based nanomedicine for PNI regeneration with improved biosafety. STATEMENT OF SIGNIFICANCE: Regardless of the fact that lithium drugs have been used in treatment of mental illness such as manic depression, the systemic side effects and renal metabolic toxicity still seriously restrict their clinical application. Since Li+ and Na+ compete for ion channels of cell membrane, the cell entry efficiency is extremely low and easily affected by body fluctuations, which seems to be an unsolvable problem. Herein, we rationally exploited the endocytotic features of CPDs to develop Li-CPDs. The Li-CPDs improved the entry pathway, greatly reduced nephrotoxicity, and inherited the biological function of Li+ to activate autophagy for promoting peripheral nerve regeneration. Due to the BBB-crossing property of Li-CPDs, it also showed application prospects in future research on central nervous system diseases.

The role of the plasmid-mediated fluoroquinolone resistance genes as resistance mechanisms in pediatric infections due to Enterobacterales.

Introduction: Fluoroquinolones (FQs) are not commonly prescribed in children, yet the increasing incidence of multidrug-resistant (MDR) Enterobacterales (Ent) infections in this population often reveals FQ resistance. We sought to define the role of FQ resistance in the epidemiology of MDR Ent in children, with an overall goal to devise treatment and prevention strategies. Methods: A case-control study of children (0-18 years) at three Chicago hospitals was performed. Cases had infections by FQ-susceptible, ß-lactamase-producing (bla) Ent harboring a non- or low-level expression of PMFQR genes (PMFQS Ent). Controls had FQR infections due to bla Ent with expressed PMFQR genes (PMFQR Ent). We sought bla genes by PCR or DNA (BD Max Check-Points assay®) and PMFQR genes by PCR. We performed rep-PCR, MLST, and E. coli phylogenetic grouping. Whole genome sequencing was additionally performed on PMFQS Ent positive isolates. Demographics, comorbidities, and device, antibiotic, and healthcare exposures were evaluated. Predictors of infection were assessed. Results: Of 170 ß-lactamase-producing Ent isolates, 85 (50%) were FQS; 23 (27%) had PMFQR genes (PMFQS cases). Eighty-five (50%) were FQR; 53 (62%) had PMFQR genes (PMFQR controls). The median age for children with PMFQS Ent and PMFQR Ent was 4.3 and 6.2 years, respectively (p = NS). Of 23 PMFQS Ent, 56% were Klebsiella spp., and of 53 PMFQR Ent, 76% were E. coli. The most common bla and PMFQR genes detected in PMFQS Ent were bla SHV ESBL (44%) and oqxAB (57%), and the corresponding genes detected in PMFQR Ent were bla CTX-M-1-group ESBL (79%) and aac(6')-Ib-cr (83%). Whole genome sequencing of PMFQS Ent revealed the additional presence of mcr-9, a transferable polymyxin resistance gene, in 47% of isolates, along with multiple plasmids and mobile genetic elements propagating drug resistance. Multivariable regression analysis showed that children with PMFQS Ent infections were more likely to have hospital onset infection (OR 5.7, 95% CI 1.6-22) and isolates containing multiple bla genes (OR 3.8, 95% CI 1.1-14.5). The presence of invasive devices mediated the effects of healthcare setting in the final model. Differences in demographics, comorbidities, or antibiotic use were not found. Conclusions: Paradoxically, PMFQS Ent infections were often hospital onset and PMFQR Ent infections were community onset. PMFQS Ent commonly co-harbored multiple bla and PMFQR genes, and additional silent, yet transferrable antibiotic resistance genes such as mcr-9, affecting therapeutic options and suggesting the need to address infection prevention strategies to control spread. Control of PMFQS Ent infections will require validating community and healthcare-based sources and risk factors associated with acquisition.

The evidence framework of traditional Chinese medicine injection (Aidi injection) in controlling malignant pleural effusion: A clustered systematic review and meta-analysis.

INTRODUCTION: Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). OBJECTIVES: We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. METHODOLOGY: All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. RESULTS: All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. CONCLUSIONS: Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.