Describing the Heterogeneity of Clinical Utilization of Congenital Syphilis Diagnostic Modalities Among Major United States Tertiary Children's Hospitals, 2017-2022.

ABSTRACT: This retrospective cohort study drawing data from 48 major tertiary children's hospitals found heterogeneity in the diagnosis and management of congenital syphilis (CS) despite CDC guideline recommendations. The noted overall rise in the number of congenital syphilis cases mirrors the nationwide increase.

Synthesis of trifluoroethoxy/aryloxy cinnolines, cinnolinones and indazoles from o-alkynylanilines via metal-free diazotization reagent.

A facile and user-friendly protocol for the synthesis of trifluoroethoxy/aryloxy cinnolines, cinnolinones and indazoles from o-alkynylaniline in good-to-excellent yields has been developed using a metal-free diazotization reagent (a combination of BF3·OEt2 and TBN). The methodology has been further extended to construct bis-cinnolinones and for the chemoselective synthesis of N-propargylated cinnolinones.

Synthesis of Indole-Fused Dihydrothiopyrano Scaffolds via (3 + 3)-Annulations of Donor-Acceptor Cyclopropanes with Indoline-2-Thiones.

A new methodology for the synthesis of N-haloindole-fused dihydrothiopyrano derivatives via (3 + 3)-annulation of donor-acceptor cyclopropanes (DACs) with indoline-2-thiones in the presence of Sc(OTf)3 as a Lewis acid catalyst has been developed. This protocol provides a variety of indole-fused dihydrothiopyrano molecules in good to excellent yields, which architecturally resemble other indole-fused tricyclic molecules having potential medicinal value. In addition, we have described a detailed reaction mechanism and transformation of the furnished product into N-fused thiazino indole molecule.

Food-grade xylitol production from corncob biomass with acute oral toxicity studies.

Xylitol, a sugar substitute, is widely used in various food formulations and finds a steady global market. In this study, xylitol crystals were produced from corncob by fermentation (as an alternative to the chemical catalytic process) by a GRAS yeast Pichia caribbica MTCC 5703 and characterized in detail for their purity and presence of any possible contaminant that may adversely affect mammalian cell growth and proliferation. The acute and chronic oral toxicity trials demonstrated no gross pathological changes with average weekly weight gain in female Wistar rats at high xylitol loading (LD50 > 10,000 mg/kg body weight). The clinical chemistry analysis supported the evidence of no dose-dependent effect by analyzing blood biochemical parameters. The finding suggests the possible application of the crystals (> 98% purity) as a food-grade ingredient for commercial manufacture pending human trials.

A metal-free BF3·OEt2 mediated chemoselective protocol for the synthesis of propargylic cyclic imines.

A chemoselective and metal/additive-free protocol for the synthesis of propargylic cyclic imine derivatives via (3 + 2)-cycloaddition of donor-acceptor cyclopropanes and alkynylnitriles in the presence of BF3·OEt2 has been established. The newly developed methodology provided access to a variety of propargylic cyclic imines in good to excellent yields. In addition, the synthesis of propargylic amines and the corresponding very stable enol derivatives from the title compound is also explored.

Pediatric Invasive Fungal Risk Score in Cancer and Hematopoietic Stem Cell Transplantation Patients With Febrile Neutropenia.

BACKGROUND: Invasive fungal diseases (IFDs) are opportunistic infections that result in significant morbidity and mortality in pediatric oncology patients. Predictive risk tools for IFD in pediatric cancer are not available. METHODS: We conducted a 7-year retrospective study of pediatric oncology patients with a diagnosis of febrile neutropenia at UCM Comer Children's Hospitals. Fourteen clinical, laboratory, and treatment-related risk factors for IFD were analyzed. Stepwise variable selection for multiple logistic regression was used to develop a risk prediction model for IFD. Two comparative analyses have been conducted: (i) all suspected IFD cases and (ii) all proven and probable IFD cases. RESULTS: A total of 667 febrile neutropenia episodes were identified in 265 patients. IFD was diagnosed in 62 episodes: 13 proven, 27 probable, and 22 possible. In the final multiple logistic regression models, 5 variables were independently significant for both analyses: fever days, neutropenia days, hypotension, and absolute lymphocyte count <250 at the time of diagnosis. The odds ratio and a relative weight for each factor were then calculated and summed to calculate a predictive score. A risk score of ≤4 and ≤5 (10/11 maximum) for each model signifies low risk, respectively (<1.2% incidence). Model discrimination was evaluated by the area under the receiver operator characteristics curve with an area under the curve of 0.95/0.94 for each model. CONCLUSION: Our prediction IFD risk models perform well, are easy-to-use, and are based on readily available clinical data. Profound lymphopenia absolute lymphocyte count <250 mm3 could serve as a new important prognostic marker for the development of IFD in pediatric cancer and hematopoietic stem cell transplant patients.

Clinical Utility of Anaerobic and Fungal Blood Cultures in the Pediatric Oncologic Population.

BACKGROUND: If there is a concern for sepsis in a pediatric patient an aerobic blood culture is obtained. A febrile or ill oncology patient will often be evaluated with aerobic, anaerobic, and fungal blood cultures. There is to our knowledge little evidence to confirm the added benefit of broadly obtaining these cultures. METHODS: A retrospective analysis of blood cultures from patients in the oncology and hematopoietic stem cell transplant wards at Children's National Medical Center between January 2010 and April 2017. Positive anaerobic and fungal cultures were evaluated for corollary positive aerobic cultures from the same time frame (+/-24 h). Unique isolates were designated as those positive anaerobic and fungal cultures without positive aerobic cultures and evaluated with detailed chart review. RESULTS: A total of 10,950 cultures were evaluated during the study period: 6579 aerobic, 2391 anaerobic cultures, 1980 fungal. In total, 419 positive aerobic, 140 positive anaerobic, and 43 positive fungal cultures were reviewed. Among these, 22 unique anaerobic cultures and 21 unique fungal cultures met case criteria. Only 7 cultures of obligate anaerobes were observed: 4 Clostridial spp., 2 Propionobacterium acnes, and 1 Peptostreptococcus spp. Thirteen of 21 fungal isolates consisted of a single colony and were regarded as probable contaminants. Penicillium, Cladosporium, and dematiaceous molds were in greatest frequency. Potential risk factors for patients with breakthrough isolates were evaluated and described. CONCLUSIONS: There is little increased yield from the use fungal and anaerobic blood cultures in addition to aerobic blood cultures in the routine evaluation of pediatric oncology and bone marrow transplant patients. Fungal and anaerobic blood cultures and should be reserved for cases with high clinical suspicion.

How I approach: the transplant recipient with fever and pulmonary infiltrates.

Recipients of hematopoietic stem cell transplants and solid organ transplants frequently develop pulmonary infiltrates from both infectious and non-infectious etiologies. Differentiation and further characterization of microbiologic etiologies-viral, bacterial, and fungal-can be exceedingly challenging. Pediatric patients face unique challenges as confirmatory evaluations with bronchoscopy or lung biopsy may be limited. A generalizable approach to diagnosing and managing these conditions has not been well established. This paper aims to summarize our initial clinical approach while discussing the relative evidence informing our practices. A pediatric patient with characteristic infiltrates who has undergone HSCT is presented to facilitate the discussion. Generalizable approaches to similar patients are highlighted as appropriate while highlighting considerations based on clinical course and key risk factors.

Assessing the Concordance of MRSA Carriage Screening With MRSA Infections.

OBJECTIVES: This study focused on children with confirmed methicillin-resistant Staphylococcus aureus (MRSA) infections to determine MRSA screening utility in guiding empirical anti-MRSA treatment of children without history of MRSA infection. We examined the concordance of screens to assess differences by infection type and used statistical analysis to determine significant contributors to concordance. METHODS: Pediatric hospital patients admitted from 2002 through 2022 were included. Subjects had MRSA infections subsequent to MRSA surveillance screens performed the preceding year. Statistical analysis identified associations between MRSA screens and infections. Number needed to treat analysis calculated the utility of rescreening. RESULTS: Among 246 subjects, 39.0% had concordant screens; 151 (61.4%) screens were obtained in the 2 weeks preceding infection. Sensitivity for bacteremia was 50.0% (n = 42), for endotracheal/respiratory 44.4% (n = 81), and 29.4% (n = 102) for skin and soft-tissue infection. For children aged younger than 6 months, sensitivity was 35.9% (n = 78). Multivariable analysis significantly associated days since screening with decreasing likelihood of concordance. Regression modeled the probability of concordance to drop below 50.0% for all infections after 4 days, after 6 days for bacteremia specifically, and 12 days for endotracheal/respiratory infections. CONCLUSIONS: The concordance of screens was far lower than negative predictive values found previously; earlier studies were possibly impacted by low prevalence and exclusion of children at high risk to inform high negative predictive values. We suggest that negative MRSA screens should not invalidate reasonable suspicion for MRSA infection in patients with high pretest probabilities.

Exploring the potential of Bacillus for crop productivity and sustainable solution for combating rice false smut disease.

Rice false smut, which is caused by the soil-borne fungal pathogen Ustilaginoidea virens (U. virens), is one of the most threatening diseases in most of the rice-growing countries including India that causes 0.5-75% yield loss, low seed germination, and a reduction in seed quality. The assessment of yield loss helps to understand the relevance of disease severity and facilitates the implementation of appropriate management strategies. This study aimed to mitigate biotic stress in rice by employing a rhizobacterial-based bioformulation, which possesses diverse capabilities as both a plant growth promoter and a biocontrol agent against U. virens. Rhizobacteria were isolated from the soil of the rice rhizospheres from the healthy plant of the false smut affected zone. Furthermore, they were identified as Bacillus strains: B. subtilis (BR_4), B. licheniformis (BU_7), B. licheniformis (BU_8), and B. vallismortis (KU_7) via sequencing. Isolates were screened for their biocontrol potential against U. virens under in vitro conditions. The antagonistic study revealed that B. vallismortis (KU_7) inhibited U. virens the most (44.6%), followed by B. subtilis BR_4 (41.4%), B. licheniformis BU_7 (39.8%), and B. licheniformis BU_8 (43.5%). Various biochemical and plant growth promoting attributes, such as phosphate and Zn solubilization, IAA, ammonium, siderophore, and chitinase production, were also investigated for all the selected isolates. Furthermore, the potential of the isolates was tested in both in vitro and field conditions by employing talc-based bioformulation through bio-priming and root treatment. The application of bioformulation revealed a 20% decrease in disease incidence in plants treated with B. vallismortis (KU_7), a 60.5% increase in the biological yield, and a 45% increase in the grain yield. This eco-friendly approach not only controlled the disease but also improved the grain quality and reduced the chaffiness.

Tunable Regio- and Stereoselective Synthesis of Z-Acrylonitrile Indoles and 3-Cyanoquinolines from 2-Alkynylanilines and Alkynylnitriles.

The merger of two bifunctional moieties, 2-alkynylaniline and alkynylnitriles, in the presence of ZnBr2 offers the tunable synthesis of two biologically important motifs: acrylonitrile indoles and 3-cyanoquinolines. The group present on the terminal alkyne of 2-alkynylaniline regulates the reaction pathways, intra- versus intermolecular, which thereby adds stereoselectivity and regioselectivity in this protocol. The conversion of an acrylonitrile indole ring to quinoline is an intriguing synthetic utility of this methodology.

De novo design of anti-variant COVID-19 vaccine.

Recent studies highlight the effectiveness of hybrid Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) vaccines combining wild-type nucleocapsid and Spike proteins. We have further enhanced this strategy by incorporating delta and omicron variants' spike protein mutations. Both delta and omicron mark the shifts in viral transmissibility and severity in unvaccinated and vaccinated patients. So their mutations are highly crucial for future viral variants also. Omicron is particularly adept at immune evasion by mutating spike epitopes. The rapid adaptations of Omicron and sub-variants to spike-based vaccines and simultaneous transmissibility underline the urgency for new vaccines in the continuous battle against SARS-CoV-2. Therefore, we have added three persistent T-cell-stimulating nucleocapsid peptides similar to homologous sequences from seasonal Human Coronaviruses (HuCoV) and an envelope peptide that elicits a strong T-cell immune response. These peptides are clustered in the hybrid spike's cytoplasmic region with non-immunogenic linkers, enabling systematic arrangement. AlphaFold (Artificial intelligence-based model building) analysis suggests omitting the transmembrane domain enhances these cytoplasmic epitopes' folding efficiency which can ensure persistent immunity for CD4+ structural epitopes. Further molecular dynamics simulations validate the compact conformation of the modeled structures and a flexible C-terminus region. Overall, the structures show stability and less conformational fluctuation throughout the simulation. Also, the AlphaFold predicted structural epitopes maintained their folds during simulation to ensure the specificity of CD4+ T-cell response after vaccination. Our proposed approach may provide options for incorporating diverse anti-viral T-cell peptides, similar to HuCoV, into linker regions. This versatility can be promising to address outbreaks and challenges posed by various viruses for effective management in this era of innovative vaccines.

Neonatal Serum Gentamicin Concentrations and Outcomes Following Maternal Once-Daily Gentamicin Dosing.

OBJECTIVE: This study evaluated newborn gentamicin serum concentrations after birth and the effects on the newborn after extended interval gentamicin dosing in peripartum mothers. METHODS: This was a single-center, retrospective chart review of neonates born to mothers that received peripartum once-daily gentamicin dosing of approximately 5 mg/kg within 12 hours of delivery. A gentamicin serum concentration was obtained immediately after birth in the newborn. The primary outcome was initial neonatal gentamicin serum concentration after birth. Several secondary outcomes were evaluated including nephrotoxicity and ototoxicity. A subgroup analysis comparing baseline demographics of mother-newborn dyads with birth neonatal serum concentrations of less than 2 mcg/mL versus 2 mcg/mL or greater was performed. RESULTS: A total of 32 mother-newborn dyads were included. Newborns had a median gestational age of 39.4 weeks and median birth weight of 3.4 kg. The mean initial gentamicin serum concentration was elevated at 3.1 ± 1.9 mcg/mL among all newborns. The median maternal dose based on actual body weight in newborns with gentamicin serum concentrations less than 2 mcg/mL was 3.5 (IQR, 3.3-4.8) mg/kg versus 4.8 (IQR, 4.3-5.2) mg/kg in those that had serum concentrations of 2 mcg/mL or greater (p = 0.025). All newborn gentamicin serum concentrations were less than 2 mcg/mL for maternal doses given less than 1 hour prior to delivery (n = 8). There were no significant differences in nephrotoxicity or ototoxicity. CONCLUSIONS: Peripartum once daily dosing of gentamicin administered between 1 to 12 hours of birth may lead to clinically significant serum concentrations in newborns.

Clinical and histopathological correlation of oral malignancy and potentially malignant disorders based on a screening program at high-risk population in Tamil Nadu, India.

Background: There is a high incidence of oral cancer and oral potential malignant disorder observed in southeast Asian countries such as India. Our study aimed to assess the correlation between screening and histopathological diagnosis and to predict the specificity and sensitivity of chair-side/field-based assessment of the oral lesion. Materials and methods: A total of 40,852 subjects aged between 20 and 60 years were screened in the 1st phase of the study, suspected lesions were stained with toluidine blue (Manufactured by Otto Chemicals private limited, India) at two time points, those who stained positively during the two points were taken up for biopsy. Provisional diagnosis was later correlated with histopathological diagnosis. Results: Subjects who underwent biopsy had a mean age of (49.01 ± 9.8 years), Leukoplakia (1.5%) was the most common lesion observed among tobacco users, interestingly it had the least correlation (39.6%) in diagnosis, Overall sensitivity (88%) and a positive predictive value (80%) was high for clinical diagnosis of OPMD in our study. Conclusion: Correlation of clinical and histopathological diagnosis observed in our study confirms higher yield of true positives while screening in remote and vulnerable populations, which would assure a better quality of life for these subjects.

Spatio-temporal expression pattern of Raffinose Synthase genes determine the levels of Raffinose Family Oligosaccharides in peanut (Arachis hypogaea L.) seed.

Raffinose family oligosaccharides (RFOs) are known to have important physiological functions in plants. However, the presence of RFOs in legumes causes flatulence, hence are considered antinutrients. To reduce the RFOs content to a desirable limit without compromising normal plant development and functioning, the identification of important regulatory genes associated with the biosynthetic pathway is a prerequisite. In the present study, through comparative RNA sequencing in contrasting genotypes for seed RFOs content at different seed maturity stages, differentially expressed genes (DEGs) associated with the pathway were identified. The DEGs exhibited spatio-temporal expression patterns with high RFOs variety showing early induction of RFOs biosynthetic genes and low RFOs variety showing a late expression at seed maturity. Selective and seed-specific differential expression of raffinose synthase genes (AhRS14 and AhRS6) suggested their regulatory role in RFOs accumulation in peanut seeds, thereby serving as promising targets in low RFOs peanut breeding programs. Despite stachyose being the major seed RFOs fraction, differential expression of raffinose synthase genes indicated the complex metabolic regulation of this pathway. The transcriptomic resource and the genes identified in this study could be studied further to develop low RFOs varieties, thus improving the overall nutritional quality of peanuts.

Anaerobic digestion of sugarcane bagasse for biogas production and digestate valorization.

Sugarcane bagasse is an abundantly available agricultural waste having high potential that is still underutilized and mostly burnt as fuel. There are various processes available for bagasse utilization in improved ways and one such process is anaerobic digestion (AD) of bagasse for biogas production. The complex structure of biomass is recalcitrant to degradation and is a major hindrance for the anaerobic digestion, so different pretreatment methods are applied to deconstruct the bagasse for microbial digestion. In this review, different processes developed for the pretreatment of bagasse and their effect on biogas production have been extensively covered. Moreover, combination of pretreatment methods, co-digestion of bagasse with other waste (nitrogen rich or easily digestible) for enhanced biogas production and biomethane generation along with other value-added products has also been reviewed. The digestate contains a significant amount of organics with partial recovery of energy and products and is generated in huge amount that further creates disposal problem. Therefore, integration of digestate valorization with AD through gasification, pyrolysis, hydrothermal carbonization and use of microalgae for maximum recovery of energy and value-added products have also been evaluated. Thus, this review highlights major emerging area of research for improvement in bagasse based processes for enhanced biogas production along with digestate valorization to make the overall process economical and sustainable.

Recent advances in black liquor valorization.

Lignocellulosic biomass is projected as a prospective renewable alternative to petroleum for the production of fuel and chemicals. Pretreatment is necessary to disrupt the lignocellulosic structure for extraction of cellulose. Biomass after pretreatment is segregated into cellulose rich solid fraction and black liquor (lignin and hemicelluloses) as a liquid stream. The plant polysaccharide-based industry primarily utilizes the cellulosic fraction as raw material, and carbon rich black liquor discarded as waste or burnt for energy recovery. This review highlights the recent advancements in the biological and chemical valorization of black liquor into fuels and chemicals. The recent research attempted for bioconversion of black liquor into Bioplastic, Biohydrogen, Biogas, and chemicals has been discussed. In addition, the efforts to replace the conventional energy recovery method with the advanced chemical process along with their modifications have been reviewed that will decide the sustainability of the lignocellulosic biomass-based industry.

Bioconversion of syringyl lignin into malic acid by Burkholderia sp. ISTR5.

Syringyl monomeric units are the most common intermediates encountered during hardwood lignin degradation. In the present study, efficient utilization of syringaldehyde (SAld), syringic acid (SAc) by Burkholderia sp. ISTR5 (R5) has been shown. The proteogenomic analysis of Burkholderia sp. ISTR5 was done to understand the enzymes involved in the degradation of syringaldehyde and syringic acid. Various proteins such as aldehyde dehydrogenase, laccase, and oxidoreductases were highly upregulated during growth on syringaldehyde and syringic acid. R5 completely transformed both the substrates SAld and SAc to other hydrocarbons in 48 h and 24 h, respectively. Moreover, bioconversion of syringyl lignins followed an unusual pathway and accumulated a considerable amount of industrially valuable chemical malic acid in the reaction titer. This study shows the robust chassis of R5 to cope with the aromatic aldehydic stress and simultaneous bioconversion into valuable products for an efficient biorefinery.

Polyhydroxyalkanoate synthesis and characterization: A proteogenomic and process optimization study for biovalorization of industrial lignin.

The strain Burkholderia sp. ISTR5 (R5) was studied for polyhydroxyalkanoate (PHA) production on Kraft lignin (KL) and lignosulfonate (LS) as substrates. During the initial screening, the maximum PHA mass fraction in biomass produced on KL and LS was 23% and 18%, respectively, at 96 h. PHA production on KL was further optimized using the Box-Behnken Design (BBD) model of Response Surface Methodology (RSM). After optimization, a 42.5% increase in PHA production and a 32.2% increase in the total cell biomass was observed. PHA was characterized by GC-MS, TEM, FTIR, NMR, and fluorescence microscopy. It was found to be a small chain length PHA with a copolymer of poly (hydroxybutyrate-co-hydroxyvalerate) (PHBV). The degradation of PHBV was also studied using this strain; it was observed that R5 completely degraded PHBV in 120 h. Genomic and proteomic analysis of R5 revealed numerous enzymes for the metabolism of lignin degradation and PHA production.

Optimizing Oral Medication Schedules for Inpatient Sleep: A Quality Improvement Intervention.

OBJECTIVES: Hospitalized children experience frequent nighttime awakenings. Oral medications are commonly administered around the clock despite the comparable efficacy of daytime administration schedules, which promote sleep. With this study, we evaluated the effectiveness of a quality improvement initiative to increase the proportion of sleep-friendly antibiotic administration schedules. METHODS: Interprofessional stakeholders modified computerized provider order entry defaults for 4 oral antibiotic medications, from around the clock to administration occurring exclusively during waking hours. Additionally, care-team members received targeted education. Outcome measures included the proportion of sleep-friendly administration schedules and patient caregiver-reported disruptions to sleep. Pre- and posteducation surveys were used to evaluate education effectiveness. Balancing measures were missed antibiotic doses and related escalations of care. RESULTS: Interrupted time series analysis revealed a 72% increase (interceptpre: 18%; interceptpost: 90%; 95% confidence interval: 65%-79%; P < .001) in intercept for percentage of orders with sleep-friendly administration schedules (orders: n pre = 1014 and n post = 649). Compared with preeducation surveys, care-team members posteducation were more likely to agree that oral medications scheduled around the clock cause sleep disruption (resident: 71% pre, 90% post [P = .01]; nurse: 63% pre, 79% post [P = .03]). Although sleep-friendly orders increased, patient caregivers reported an increase in sleep disruption due to medications (pre 28%, post 46%; P < .001). CONCLUSIONS: A simple, low-cost intervention of computerized provider order entry default modifications and education can increase the proportion of sleep-friendly oral antibiotic administration schedules for hospitalized children. Patient perception of sleep is impacted by multiple factors and often does not align with objective data. An increased focus on improving sleep during hospitalization may result in heightened awareness of disruptions.