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Objective: Computerized clinical decision support (CDS) assists healthcare professionals in making decisions to improve patient care. In the realms of antimicrobial stewardship (ASP) and infection prevention (IP) programs, CDS interventions can play a crucial role in optimizing antibiotic prescribing practices, reducing healthcare-associated infections, and promoting diagnostic stewardship when optimally designed. This primer article aims to provide ASP and IP professionals with a practical framework for the development, design, and evaluation of CDS interventions., Setting: Large academic medical center design: Established frameworks of CDS evaluation, "Five Rights" of CDS and the "Ten Commandments of Effective Clinical Decision Support", were applied to two real-world examples of CDS tools, a Vancomycin Best Practice Advisory and a Clostridioides Difficile order panel, to demonstrate a structured approach to developing and enhancing the functionality of ASP/IP CDS interventions to promote efficacy and reduce unintended consequences of CDS., Conclusions: By outlining a structured approach for the development and evaluation of CDS interventions, with focus on end user engagement, efficiency and feasibility, ASP and IP professionals can leverage CDS to enhance IP/ASP quality improvement initiatives aimed to improve antibiotic utilization, diagnostic stewardship, and adherence to IP protocols., Competing Interests: None., (© The Author(s) 2024.)

This retrospective cohort study analyzed differences in rates of central line-associated bloodstream infections (CLABSI) in Black and White inpatients across 11 southeastern US hospitals from 2019 to 2021. Results showed higher CLABSI rates in Black patients during the coronavirus disease 2019 (COVID-19) pandemic, even after adjustment for COVID-19 infection and clinical factors.

To visualize the cellular and subcellular localization of neuromodulatory G-protein-coupled receptors in Drosophila , we implement a molecular strategy recently used to add epitope tags to ionotropic receptors at their endogenous loci. Leveraging evolutionary conservation to identify sites more likely to permit insertion of a tag, we generated constitutive and conditional tagged alleles for Drosophila 5-HT1A , 5-HT2A , 5-HT2B , Oct β 1R , Oct β 2R , two isoforms of OAMB , and mGluR The conditional alleles allow for the restricted expression of tagged receptor in specific cell types, an option not available for any previous reagents to label these proteins. We show expression patterns for these receptors in female brains and that 5-HT1A and 5-HT2B localize to the mushroom bodies (MBs) and central complex, respectively, as predicted by their roles in sleep. By contrast, the unexpected enrichment of Octβ1R in the central complex and of 5-HT1A and 5-HT2A to nerve terminals in lobular columnar cells in the visual system suggest new hypotheses about their functions at these sites. Using an additional tagged allele of the serotonin transporter, a marker of serotonergic tracts, we demonstrate diverse spatial relationships between postsynaptic 5-HT receptors and presynaptic 5-HT neurons, consistent with the importance of both synaptic and volume transmission. Finally, we use the conditional allele of 5-HT1A to show that it localizes to distinct sites within the MBs as both a postsynaptic receptor in Kenyon cells and a presynaptic autoreceptor., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Human exposure to the metal lead (Pb) is prevalent and associated with adverse neurodevelopmental and neurodegenerative outcomes. Pb disrupts normal brain function by inducing oxidative stress and neuroinflammation, altering cellular metabolism, and displacing essential metals. Prior studies on the molecular impacts of Pb have examined bulk tissues, which collapse information across all cell types, or in targeted cells, which are limited to cell autonomous effects. These approaches are unable to represent the complete biological implications of Pb exposure because the brain is a cooperative network of highly heterogeneous cells, with cellular diversity and proportions shifting throughout development, by brain region, and with disease. New technologies are necessary to investigate whether Pb and other environmental exposures alter cell composition in the brain and whether they cause molecular changes in a cell-type-specific manner. Cutting-edge, single-cell approaches now enable research resolving cell-type-specific effects from bulk tissues. This article reviews existing Pb neurotoxicology studies with genome-wide molecular signatures and provides a path forward for the field to implement single-cell approaches with practical recommendations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kelly Bakulski reports financial support was provided by National Institutes of Health.

Background: Penicillin's long-standing role as the reference standard in syphilis treatment has led to global reliance. However, this dependence presents challenges, prompting the need for alternative strategies. We performed a systematic literature review and meta-analysis to evaluate the efficacy of these alternative treatments against nonneurological syphilis., Methods: We searched MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane, Scopus, and Web of Science from database inception to 28 August 2023, and we included studies that compared penicillin or amoxicillin monotherapy to other treatments for the management of nonneurological syphilis. Our primary outcome was serological cure rates. Random-effect models were used to obtain pooled mean differences, and heterogeneity was assessed using the I 2 test., Results: Of 6478 screened studies, 27 met the inclusion criteria, summing 6710 patients. The studies were considerably homogeneous, and stratified analyses considering each alternative treatment separately revealed that penicillin monotherapy did not outperform ceftriaxone (pooled odds ratio, 1.66 [95% confidence interval, .97-2.84]; I 2 = 0%), azithromycin (0.92; [.73-1.18]; I 2 = 0%), or doxycycline (0.82 [.61-1.10]; I 2 = 1%) monotherapies with respect to serological conversion., Conclusions: Alternative treatment strategies have serological cure rates equivalent to penicillin, potentially reducing global dependence on this antibiotic., Competing Interests: Potential conflicts of interest. All authors report no conflicts of interest relevant to this article., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Lumbar vertebral tuberculosis presenting with a focal solitary osteolytic lesion is rare in spinal tuberculosis (TB) and the English literature describing this entity is scant. The differential diagnosis includes primary and secondary malignancies. In this report, we describe a case of 35-year-old woman who presented with low back pain and was found to have a focal L4 vertebral lytic lesion on MRI and CT. Whole body CT was carried out as a potential malignancy staging procedure and demonstrated lung lesions suggestive of TB. Her neurological and general examination were entirely normal. Her blood test was positive for QuantiFERON Gold. She was managed conservatively with anti-TB medications and serial imaging which showed evidence of resolution of the osteolytic lesion. Although it is unusual for TB to present as an isolated osteolytic vertebral body lesion, the possibility should always be considered in the differential diagnosis, along with neoplastic processes. Conservative medical management, in the absence of neurological deficits and deformity, is the main stay of management with a very good outlook.

Extrinsic signaling between diverse cell types is crucial for nervous system development. Ligand binding is a key driver of developmental processes. Nevertheless, it remains a significant challenge to disentangle which and how extrinsic signals act cooperatively to affect changes in recipient cells. In the developing human brain, cortical progenitors transition from neurogenesis to gliogenesis in a stereotyped sequence that is in part influenced by extrinsic ligands. Here we used published transcriptomic data to identify and functionally test five ligand-receptor pairs that synergistically drive human astrogenesis. We validate the synergistic contributions of TGFβ2, NLGN1, TSLP, DKK1 and BMP4 ligands on astrocyte development in both hCOs and primary fetal tissue. We confirm that the cooperative capabilities of these five ligands are greater than their individual capacities. Additionally, we discovered that their combinatorial effects converge in part on the mTORC1 signaling pathway, resulting in transcriptomic and morphological features of astrocyte development. Our data-driven framework can leverage single-cell and bulk genomic data to generate and test functional hypotheses surrounding cell-cell communication regulating neurodevelopmental processes., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: An mpox (formerly "monkeypox") outbreak began in 2022, leading to infection in special populations, including pregnant individuals., Case: We present a case of an individual who presented with a labial ulcer and subsequent papular rash at 31 weeks of gestation. She was diagnosed with mpox infection and was treated with tecovirimat. She had an uncomplicated induction of labor at 39 2/7 weeks of gestation and delivered a healthy neonate. The neonate had a positive immunoglobulin G test result for orthopoxvirus but did not have skin lesions or positive molecular test results suggestive of infection., Conclusion: Transplacental transmission of mpox is possible, but, in this case, the neonate did not have clinical findings suggestive of active or antenatal mpox infection. Treatment with tecovirimat in gestational cases of mpox may be beneficial., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. The mechanisms by which inhibition of SERT activity influences behavior are poorly understood. To address this question in the model organism Drosophila melanogaster, we developed new loss of function mutations in Drosophila SERT (dSERT). Previous studies in both flies and mammals have implicated serotonin as an important neuromodulator of sleep, and our newly generated dSERT mutants show an increase in total sleep and altered sleep architecture that is mimicked by feeding the SSRI citalopram. Differences in daytime versus nighttime sleep architecture as well as genetic rescue experiments unexpectedly suggest that distinct serotonergic circuits may modulate daytime versus nighttime sleep. dSERT mutants also show defects in copulation and food intake, akin to the clinical side effects of SSRIs and consistent with the pleomorphic influence of serotonin on the behavior of D. melanogaster. Starvation did not overcome the sleep drive in the mutants and in male dSERT mutants, the drive to mate also failed to overcome sleep drive. dSERT may be used to further explore the mechanisms by which serotonin regulates sleep and its interplay with other complex behaviors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Knapp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Estimates of the case hospitalization rate and case fatality rate when hospital care is available for monkeypox (MPX) infections have not been well defined. This rapid systematic review and meta-analysis aimed to estimate the case hospitalisation rate and case fatality rate where hospital care is available., Methods: We systematically searched PubMed, Embase, the Lancet Preprints, and MedRxiv for studies published between Jan 1, 1950 and Aug 2, 2022. We included documents which contained both the number of cases and associated hospitalisations of MPX infections. From eligible studies we extracted the country, the year of the study, the study design type, the clade of MPX, the participant characteristics, transmission type, any treatments used, number of cases (including suspected, probable, or laboratory confirmed diagnosis), number of hospitalizations, hospitalized patient outcomes, and case definition. Case hospitalization rate (CHR) was defined as the proportion of cases that were admitted to hospital care while case fatality rate (CFR) was defined as the proportion of cases that died. CHR and CFR were analysed in a fully Bayesian meta-analytic framework using random effects models, including sub-group analysis with heterogeneity assessed using I 2 ., Findings: Of the 259 unique documents identified, 19 studies were eligible for inclusion. Included studies represented 7553 reported cases among which there were 555 hospitalizations. Of the 7540 cases for which outcomes were available, there were 15 recorded deaths. The median age of cases was 35 years (interquartile range 28-38, n = 2010) and primarily male (7339/7489, 98%) in studies where age or sex were available. Combined CHR was estimated to be 14.1% (95% credible interval, 7.5-25.0, I 2 97.4%), with a high degree of heterogeneity. Further analysis by outbreak period indicates CHRs of 49.8% (28.2-74.0, I 2 81.4%), 21.7% (7.2-52.1, I 2 57.7%), and 5.8% (3.2-9.4, I 2 92.4%) during the pre-2017, 2017-2021, and 2022 outbreaks, respectively, again with high levels of heterogeneity. CFR was estimated to be 0.03% (0.0-0.44, I 2 99.9%), with evidence of large heterogeneity between the studies., Interpretation: There is limited data for MPX hospitalization rates in countries where MPX has been traditionally non-endemic until the current outbreak. Due to substantial heterogeneity, caution is needed when interpreting these findings. Health care organizations should be cognizant of the potential increase in healthcare utilization. Rapid identification of infection and use of appropriate therapies such as antivirals play a role reducing the CHR and associated CFR., Funding: None., Competing Interests: CJM acknowledges support from BINX, 10.13039/100012399Biomedical Advanced Research and Development Authority, 10.13039/100004330GlaxoSmithKline, Becton Dickinson, United States Center for Disease Control and Prevention, 10.13039/100017037Cepheid, Gilead, 10.13039/100015160Hologic, Lupin, National Association of County and City Health Officials, and 10.13039/100000002National Institutes of Health paid to her employer., (© 2022 The Author(s).)

In this study, we used genomic sequencing to identify variants of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in healthcare workers with coronavirus disease 2019 (COVID-19) after receiving a booster vaccination. We compared symptoms, comorbidities, exposure risks, and vaccine history between the variants. Postbooster COVID-19 cases increased as the SARS-CoV-2 omicron variant predominated., (© The Author(s) 2022.)

Single-nuclei RNA sequencing characterizes cell types at the gene level. However, compared to single-cell approaches, many single-nuclei cDNAs are purely intronic, lack barcodes and hinder the study of isoforms. Here we present single-nuclei isoform RNA sequencing (SnISOr-Seq). Using microfluidics, PCR-based artifact removal, target enrichment and long-read sequencing, SnISOr-Seq increased barcoded, exon-spanning long reads 7.5-fold compared to naive long-read single-nuclei sequencing. We applied SnISOr-Seq to adult human frontal cortex and found that exons associated with autism exhibit coordinated and highly cell-type-specific inclusion. We found two distinct combination patterns: those distinguishing neural cell types, enriched in TSS-exon, exon-polyadenylation-site and non-adjacent exon pairs, and those with multiple configurations within one cell type, enriched in adjacent exon pairs. Finally, we observed that human-specific exons are almost as tightly coordinated as conserved exons, implying that coordination can be rapidly established during evolution. SnISOr-Seq enables cell-type-specific long-read isoform analysis in human brain and in any frozen or hard-to-dissociate sample., (© 2022. The Author(s).)

Skin and soft tissue infections are common in diabetics. Diabetic foot infection usually results from disruption of the skin barrier, trauma, pressure, or ischemic wounds. These wounds may become secondarily infected or lead to development of adjacent soft tissue or deeper bone infection. Clinical assessment and diagnosis of these conditions using a multidisciplinary management approach, including careful attention to antibiotic selection, lead to the best outcomes in patient care., Competing Interests: Disclosure C. Polk has received research funding from Merck, United States., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Sensory systems rely on neuromodulators, such as serotonin, to provide flexibility for information processing as stimuli vary, such as light intensity throughout the day. Serotonergic neurons broadly innervate the optic ganglia of Drosophila melanogaster, a widely used model for studying vision. It remains unclear whether serotonin modulates the physiology of interneurons in the optic ganglia. To address this question, we first mapped the expression patterns of serotonin receptors in the visual system, focusing on a subset of cells with processes in the first optic ganglion, the lamina. Serotonin receptor expression was found in several types of columnar cells in the lamina including 5-HT2B in lamina monopolar cell L2, required for spatiotemporal luminance contrast, and both 5-HT1A and 5-HT1B in T1 cells, whose function is unknown. Subcellular mapping with GFP-tagged 5-HT2B and 5-HT1A constructs indicated that these receptors localize to layer M2 of the medulla, proximal to serotonergic boutons, suggesting that the medulla neuropil is the primary site of serotonergic regulation for these neurons. Exogenous serotonin increased basal intracellular calcium in L2 terminals in layer M2 and modestly decreased the duration of visually induced calcium transients in L2 neurons following repeated dark flashes, but otherwise did not alter the calcium transients. Flies without functional 5-HT2B failed to show an increase in basal calcium in response to serotonin. 5-HT2B mutants also failed to show a change in amplitude in their response to repeated light flashes but other calcium transient parameters were relatively unaffected. While we did not detect serotonin receptor expression in L1 neurons, they, like L2, underwent serotonin-induced changes in basal calcium, presumably via interactions with other cells. These data demonstrate that serotonin modulates the physiology of interneurons involved in early visual processing in Drosophila., Competing Interests: The authors have declared that no competing interests exist.

Patients with prolonged neutropenia are at risk for a variety of complications and infections including the development of mucositis and oral ulcers. The changes in oral flora during chemotherapy and its effects on the development of infections of the oral cavity have been studied with inconsistent results. However, there is evidence that supports the colonization of gram negative rods in patients undergoing chemotherapy. In this report, we present two leukemic patients who developed oral ulcers secondary to multi-drug resistant Pseudomonas aeruginosa. It is important to suspect multi-drug resistant gram negative rods in patients with prolonged neutropenia who develop gum infections despite appropriate antibiotic coverage.

Introduction: A significant portion of the increased risk of cancer and respiratory disease from exposure to cigarette smoke is attributed to volatile organic compounds (VOCs). In this study, 21 VOCs were quantified in mainstream cigarette smoke from 50U.S. domestic brand varieties that included high market share brands and 2 Kentucky research cigarettes (3R4F and 1R5F)., Methods: Mainstream smoke was generated under ISO 3308 and Canadian Intense (CI) smoking protocols with linear smoking machines with a gas sampling bag collection followed by solid phase microextraction/gas chromatography/mass spectrometry (SPME/GC/MS) analysis., Results: For both protocols, mainstream smoke VOC amounts among the different brand varieties were strongly correlated between the majority of the analytes. Overall, Pearson correlation (r) ranged from 0.68 to 0.99 for ISO and 0.36 to 0.95 for CI. However, monoaromatic compounds were found to increase disproportionately compared to unsaturated, nitro, and carbonyl compounds under the CI smoking protocol where filter ventilation is blocked., Conclusions: Overall, machine generated "vapor phase" amounts (µg/cigarette) are primarily attributed to smoking protocol (e.g., blocking of vent holes, puff volume, and puff duration) and filter ventilation. A possible cause for the disproportionate increase in monoaromatic compounds could be increased pyrolysis under low oxygen conditions associated with the CI protocol., Implications: This is the most comprehensive assessment of volatile organic compounds (VOCs) in cigarette smoke to date, encompassing 21 toxic VOCs, 50 different cigarette brand varieties, and 2 different machine smoking protocols (ISO and CI). For most analytes relative proportions remain consistent among U.S. cigarette brand varieties regardless of smoking protocol, however the CI smoking protocol did cause up to a factor of 6 increase in the proportion of monoaromatic compounds. This study serves as a basis to assess VOC exposure as cigarette smoke is a principle source of overall population-level VOC exposure in the United States., (Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

In vivo microdialysis is widely used to investigate how neurotransmitter levels in the brain respond to biologically relevant challenges. Here, we combined recent improvements in the temporal resolution of online sampling and analysis for serotonin with a brief high-K(+) stimulus paradigm to study the dynamics of evoked release. We observed stimulated serotonin overflow with high-K(+) pulses as short as 1 min when determined with 2-min dialysate sampling in ventral striatum. Stimulated serotonin levels in female mice during the high estrogen period of the estrous cycle were similar to serotonin levels in male mice. By contrast, stimulated serotonin overflow during the low estrogen period in female mice was increased to levels similar to those in male mice with local serotonin transporter (SERT) inhibition. Stimulated serotonin levels in mice with constitutive loss of SERT were considerably higher yet, pointing to neuroadaptive potentiation of serotonin release. When combined with brief K(+) stimulation, fast microdialysis reveals dynamic changes in extracellular serotonin levels associated with normal hormonal cycles and pharmacologic vs genetic loss of SERT function.

Quantifying volatile organic compounds (VOCs) in cigarette smoke is necessary to establish smoke-related exposure estimates and evaluate emerging products and potential reduced-exposure products. In response to this need, we developed an automated, multi-VOC quantification method for machine-generated, mainstream cigarette smoke using solid-phase microextraction gas chromatography-mass spectrometry (SPME-GC-MS). This method was developed to simultaneously quantify a broad range of smoke VOCs (i.e., carbonyls and volatiles, which historically have been measured by separate assays) for large exposure assessment studies. Our approach collects and maintains vapor-phase smoke in a gas sampling bag, where it is homogenized with isotopically labeled analogue internal standards and sampled using gas-phase SPME. High throughput is achieved by SPME automation using a CTC Analytics platform and custom bag tray. This method has successfully quantified 22 structurally diverse VOCs (e.g., benzene and associated monoaromatics, aldehydes and ketones, furans, acrylonitrile, 1,3-butadiene, vinyl chloride, and nitromethane) in the microgram range in mainstream smoke from 1R5F and 3R4F research cigarettes smoked under ISO (Cambridge Filter or FTC) and Intense (Health Canada or Canadian Intense) conditions. Our results are comparable to previous studies with few exceptions. Method accuracy was evaluated with third-party reference samples (≤15% error). Short-term diffusion losses from the gas sampling bag were minimal, with a 10% decrease in absolute response after 24 h. For most analytes, research cigarette inter- and intrarun precisions were ≤20% relative standard deviation (RSD). This method provides an accurate and robust means to quantify VOCs in cigarette smoke spanning a range of yields that is sufficient to characterize smoke exposure estimates.