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American Journal of Health-system... Jul 2024In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been...
Optimizing discharge antimicrobial therapy: Evaluation of a transitions of care process and electronic scoring system for patients with community-acquired pneumonia or chronic obstructive pulmonary disease.
DISCLAIMER
In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
PURPOSE
Prescribing excess antibiotic duration at hospital discharge is common. A pharmacist-led Antimicrobial Stewardship Program Transition of Care (ASP TOC) intervention was associated with improved discharge prescribing. To improve the sustainability of this service, an electronic scoring system (ESS), which included the ASP TOC electronic variable, was implemented in the electronic medical record to prioritize pharmacist workload. The purpose of this study was to evaluate the implementation of the ASP TOC variable in the ESS in patients with community-acquired pneumonia (CAP) or chronic obstructive pulmonary disease (COPD).
METHODS
This institutional review board-approved, retrospective quasi-experiment included patients discharged on oral antibiotics for CAP or COPD exacerbation (lower respiratory tract infection) from November 1, 2021, to March 1, 2022 (the preintervention period) and November 1, 2022, to March 1, 2023 (the postintervention period). The primary endpoint was optimized discharge antimicrobial regimen. A sample of at least 194 patients was required to achieve 80% power to detect a 20% difference in the frequency of optimized therapy. Multivariable logistic regression was used to identify factors associated with optimized regimens.
RESULTS
Similar baseline characteristics were observed in both study groups (n = 100 for both groups). The frequency of optimized discharge regimens improved from 69% to 82% (P = 0.033). The percentage of ASP TOC interventions documented as completed by a pharmacist increased from 4% to 25% (P < 0.001). ASP TOC intervention, female gender, and COPD were independently associated with an optimized discharge regimen (adjusted odds ratios, 6.57, 1.61, and 3.89, respectively; 95% CI, 1.51-28.63, 0.81-3.17, and 1.85-8.20, respectively).
CONCLUSION
After the launch of the ASP TOC variable, there was an increase in optimized discharge regimens and ASP TOC interventions completed. Pharmacists' use of the ASP TOC variable through an ESS can aid in improving discharge prescribing.
PubMed: 38953520
DOI: 10.1093/ajhp/zxae174 -
MBio Jul 2024Nasopharyngeal carriage of staphylococci spreads potentially pathogenic strains into (peri)oral regions and increases the chance of cross-infections. Some laboratory...
UNLABELLED
Nasopharyngeal carriage of staphylococci spreads potentially pathogenic strains into (peri)oral regions and increases the chance of cross-infections. Some laboratory strains can also move rapidly on hydrated agar surfaces, but the biological relevance of these observations is not clear. Using soft-agar [0.3% (wt/vol)] plate assays, we demonstrate the rapid surface dispersal of (peri)oral isolates of and and closely related laboratory strains in the presence of mucin glycoproteins. Mucin-induced dispersal was a stepwise process initiated by the passive spreading of the growing colonies followed by their rapid branching (dendrites) from the colony edge. Although most spreading strains used mucin as a growth substrate, dispersal was primarily dependent on the lubricating and hydrating properties of the mucins. Using JE2 as a genetically tractable representative, we demonstrate that mucin-induced dendritic dispersal, but not colony spreading, is facilitated by the secretion of surfactant-active phenol-soluble modulins (PSMs) in a process regulated by the quorum-sensing system. Furthermore, the dendritic dispersal of JE2 colonies was further stimulated in the presence of surfactant-active supernatants recovered from the most robust (peri)oral spreaders of and . These findings suggest complementary roles for lubricating mucins and staphylococcal PSMs in the active dispersal of potentially pathogenic strains from perioral to respiratory mucosae, where gel-forming, hydrating mucins abound. They also highlight the impact that interspecies interactions have on the co-dispersal of with other perioral bacteria, heightening the risk of polymicrobial infections and the severity of the clinical outcomes.
IMPORTANCE
Despite lacking classical motility machinery, nasopharyngeal staphylococci spread rapidly in (peri)oral and respiratory mucosa and cause cross-infections. We describe laboratory conditions for the reproducible study of staphylococcal dispersal on mucosa-like surfaces and the identification of two dispersal stages (colony spreading and dendritic expansion) stimulated by mucin glycoproteins. The mucin type mattered as dispersal required the surfactant activity and hydration provided by some mucin glycoproteins. While colony spreading was a passive mode of dispersal lubricated by the mucins, the more rapid and invasive form of dendritic expansion of and required additional lubrication by surfactant-active peptides (phenol-soluble modulins) secreted at high cell densities through quorum sensing. These results highlight a hitherto unknown role for gel-forming mucins in the dispersal of staphylococcal strains associated with cross-infections and point at perioral regions as overlooked sources of carriage and infection by staphylococci.
PubMed: 38953351
DOI: 10.1128/mbio.01562-24 -
Human Vaccines & Immunotherapeutics Dec 2024Many pathogens enter the host through mucosal sites. Thus, interfering with pathogen entry through local neutralization at mucosal sites therefore is an effective... (Review)
Review
Many pathogens enter the host through mucosal sites. Thus, interfering with pathogen entry through local neutralization at mucosal sites therefore is an effective strategy for preventing disease. Mucosally administered vaccines have the potential to induce protective immune responses at mucosal sites. This manuscript delves into some of the latest developments in mucosal vaccination, particularly focusing on advancements in adjuvant technologies and the role of these adjuvants in enhancing vaccine efficacy against respiratory pathogens. It highlights the anatomical and immunological complexities of the respiratory mucosal immune system, emphasizing the significance of mucosal secretory IgA and tissue-resident memory T cells in local immune responses. We further discuss the differences between immune responses induced through traditional parenteral vaccination approaches vs. mucosal administration strategies, and explore the protective advantages offered by immunization through mucosal routes.
Topics: Humans; Immunity, Mucosal; Respiratory Mucosa; Animals; Vaccines; Administration, Mucosal; Adjuvants, Vaccine; Vaccination; Adjuvants, Immunologic; Respiratory Tract Infections; Memory T Cells; Immunoglobulin A, Secretory
PubMed: 38953250
DOI: 10.1080/21645515.2024.2368288 -
Frontiers in Immunology 2024P2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and...
INTRODUCTION
P2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and have been involved in similar physiological processes, such as pain and inflammation as well as various immune cell functions. While formation of P2X2/P2X3 heterotrimers produces a distinct pharmacological phenotype and has been well established, functional identification of a P2X4/P2X7 heteromer has been difficult and evidence for and against a physical association has been found. Most of this evidence stems, however, from model systems.
METHODS
Here, we used a P2X7-EGFP BAC transgenic mouse model as well as P2X4 and P2X7 knock-out mice to re-investigate a P2X4-P2X7 interaction in mouse lung by biochemical and immunohistochemical experiments as well as quantitative expression analysis.
RESULTS
No detectable amounts of P2X4 could be co-purified from mouse lung via P2X7-EGFP. In agreement with these findings, immuno-histochemical analysis using a P2X7-specific nanobody revealed only limited overlap in the cellular and subcellular localizations of P2X4 and P2X7 in both the native lung tissue and primary cells. Comparison of P2X4 and P2X7 transcript and protein levels in the respective gene-deficient and wild type mice showed no mutual interrelation between their expression levels in whole lungs. However, a significantly reduced expression was found in alveolar macrophages of mice.
DISCUSSION
In summary, our detailed analysis of the cellular and subcellular P2X4 and P2X7 localization and expression does not support a physiologically relevant direct association of P2X4 and P2X7 subunits or receptors .
Topics: Animals; Receptors, Purinergic P2X4; Receptors, Purinergic P2X7; Mice; Lung; Mice, Knockout; Mice, Transgenic; Mice, Inbred C57BL; Protein Binding
PubMed: 38953020
DOI: 10.3389/fimmu.2024.1425938 -
BioRxiv : the Preprint Server For... May 2024COVID-19 significantly decreases amino acids, fatty acids, and most eicosanoidsSARS-CoV-2 preferentially localizes to central lung tissueMetabolic disturbance is highest...
COVID-19 significantly decreases amino acids, fatty acids, and most eicosanoidsSARS-CoV-2 preferentially localizes to central lung tissueMetabolic disturbance is highest in peripheral tissue, not central like viral loadSpatial metabolomics allows detection of metabolites not altered overallSARS-CoV-2, the virus responsible for COVID-19, is a highly contagious virus that can lead to hospitalization and death. COVID-19 is characterized by its involvement in the lungs, particularly the lower lobes. To improve patient outcomes and treatment options, a better understanding of how SARS-CoV-2 impacts the body, particularly the lower respiratory system, is required. In this study, we sought to understand the spatial impact of COVID-19 on the lungs of mice infected with mouse-adapted SARS2-N501Y . Overall, infection caused a decrease in fatty acids, amino acids, and most eicosanoids. When analyzed by segment, viral loads were highest in central lung tissue, while metabolic disturbance was highest in peripheral tissue. Infected peripheral lung tissue was characterized by lower levels of fatty acids and amino acids when compared to central lung tissue. This study highlights the spatial impacts of SARS-CoV-2 and helps explain why peripheral lung tissue is most damaged by COVID-19.
PubMed: 38952797
DOI: 10.1101/2024.05.22.595414 -
The Canadian Veterinary Journal = La... Jul 2024A swine production system had 3 sections located a few kilometers apart. Sections A and C contained several thousand sows and nursery and finishing pigs. Section B,...
A swine production system had 3 sections located a few kilometers apart. Sections A and C contained several thousand sows and nursery and finishing pigs. Section B, located between the other 2 sections, was the smallest and had 6 finishing sites and 2 sow sites. The entire system was infected with porcine reproductive and respiratory syndrome virus, , and Section B was depopulated, cleaned, disinfected, and repopulated with negative gilts. Despite extreme measures, recontamination occurred for each pathogen, with aerosol considered the most plausible contamination source.
Topics: Animals; Swine; Aerosols; Swine Diseases; Mycoplasma hyopneumoniae; Actinobacillus pleuropneumoniae; Porcine respiratory and reproductive syndrome virus; Actinobacillus Infections; Pneumonia of Swine, Mycoplasmal; Female; Porcine Reproductive and Respiratory Syndrome; Animal Husbandry
PubMed: 38952762
DOI: No ID Found -
Oncoimmunology 2024Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive...
Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8 T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8 T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified , as a candidate gene expressed by tumor-specific T cells. In addition to expressing , tumor-specific T cells were present in a higher proportion of T cells co-expressing (PD-1)/(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients ( = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8 T cells in MPE, which are associated with patients' prognosis. (233 words).
Topics: Humans; Lung Neoplasms; CD8-Positive T-Lymphocytes; Pleural Effusion, Malignant; Single-Cell Analysis; Receptors, Antigen, T-Cell; T-Lymphocyte Subsets; Male; Female; Middle Aged; Aged; Antigens, Neoplasm
PubMed: 38952674
DOI: 10.1080/2162402X.2024.2371556 -
Cureus Jun 2024Background MXene is a newly discovered substance consisting of 2D transition metal carbides or nitrides, produced through the disintegration and etching of aluminum...
Background MXene is a newly discovered substance consisting of 2D transition metal carbides or nitrides, produced through the disintegration and etching of aluminum layers. It possesses numerous properties, including a high surface area, conductivity, strength, stiffness, negative zeta potential, and excellent volumetric capacitance. MXene is utilized in detecting anti-cancer medicine, while bismuth vanadate (BiVO) is synthesized to form an optimized material for anti-cancer activity applications. BiVO exhibits visible light absorption, strong chemical stability, and non-toxic properties. However, when loaded onto target stem cells, it can cause skin and respiratory irritation. Aim This study aimed to evaluate the facile fabrication of titanium carbide (TiC)-BiVO nanomaterials coupled with oxides for anti-cancer activity. Moreover, it aimed to create TiC-BiVO nanomaterials in combination with oxides using X-ray diffraction (XRD) and scanning electron microscopy (SEM) to assess their potential as efficient and targeted anti-cancer agents. Methods and materials To prepare the 2D TiC MXene, 2.5 g of titanium aluminum carbide (TiAlC) powder was dissolved in 60 mL of a 40% hydrofluoric acid (HF) solution in a polytetrafluoroethylene(PTFE) container. The etching process was made more efficient and completed in 24 hours by using a magnetic stirring system to keep the mixture stirred and heated continuously. The centrifugation was performed at 4000 rpm for five minutes. Subsequently, deionized water was used to wash the solution many times until its pH reached around 7. The appropriate TiC powder was made by vacuum drying the acquired sediment at 80°C for 24 hours. Monoclinic BiVO samples were synthesized via a hydrothermal method. Typically, 10 mmol of Bi(NO).5HO was dissolved in 100 mL of a 2 mol/L HNO solution and stirred uniformly. Subsequently, 10 mmol of ammonium metavanadate (NHVO) was added to the mixed solution. After being stirred for one hour, the mixture was transferred into a 100 mL sealed Teflon-lined stainless steel autoclave at 180°C for 16 hours. After cooling to room temperature, the sediment was washed three times with deionized water, ethanol, and acetone, respectively. Finally, the suspension was dried at 80°C, followed by calcination at 450°C for three hours to obtain BiVO. TiC-BiVO heterostructures were prepared by surface modification TiCusing BiVO suspensions by a simple, cost-effective approach. Results TiC nanosheets were observed with BiVO particles, and the high crystalline nature of the compound was confirmed after XRD analysis and energy-dispersive spectroscopy (EDS) analysis. The compound was found to be pure without any impurities and exhibited anti-cancer activity. Conclusion The XRD, field emission scanning electron microscopy(FESEM), and EDS investigations provide an in-depth analysis of the structural, morphological, and compositional characteristics of TiC-BiVO sheets. The XRD analysis proves the successful combination of different materials and the presence of crystalline phases. The FESEM imaging technique exposes the shape and arrangement of particles in sheets, while the EDS analysis verifies the elemental composition and uniform distribution. These investigations show that TiC-BiVO composites have been successfully synthesized, indicating their potential for use in anti-cancer applications.
PubMed: 38952587
DOI: 10.7759/cureus.61492 -
Frontiers in Neurology 2024Sleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female...
24-h continuous non-invasive multiparameter home monitoring of vitals in patients with Rett syndrome by an innovative wearable technology: evidence of an overlooked chronic fatigue status.
BACKGROUND
Sleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female patients) linked to pathogenic variations in the X-linked methyl-CpG-binding protein 2 () gene. Autonomic nervous system dysfunction with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT, along with exercise fatigue and increased sudden death risk. The aim of the present study was to test the feasibility of a continuous 24 h non-invasive home monitoring of the biological vitals (biovitals) by an innovative wearable sensor device in pediatric and adolescent/adult RTT patients.
METHODS
A total of 10 female patients (mean age 18.3 ± 9.4 years, range 4.7-35.5 years) with typical RTT and pathogenic variations were enrolled. Clinical severity was assessed by validated scales. Heart rate (HR), respiratory rate (RR), and skin temperature (SkT) were monitored by the YouCare Wearable Medical Device (Accyourate Group SpA, L'Aquila, Italy). The average percentage of maximum HR (HRmax%) was calculated. Heart rate variability (HRV) was expressed by consolidated time-domain and frequency-domain parameters. The HR/LF (low frequency) ratio, indicating SNS activation under dynamic exercise, was calculated. Simultaneous continuous measurement of indoor air quality variables was performed and the patients' contributions to the surrounding water vapor partial pressure [P (pt)] and carbon dioxide [P (pt)] were indirectly estimated.
RESULTS
Of the 6,559.79 h of biovital recordings, 5051.03 h (77%) were valid for data interpretation. Sleep and wake hours were 9.0 ± 1.1 h and 14.9 ± 1.1 h, respectively. HRmax % [median: 71.86% (interquartile range 61.03-82%)] and HR/LF [median: 3.75 (interquartile range 3.19-5.05)] were elevated, independent from the wake-sleep cycle. The majority of HRV time- and frequency-domain parameters were significantly higher in the pediatric patients ( ≤ 0.031). The HRV HR/LF ratio was associated with phenotype severity, disease progression, clinical sleep disorder, subclinical hypoxia, and electroencephalographic observations of multifocal epileptic activity and general background slowing.
CONCLUSION
Our findings indicate the feasibility of a continuous 24-h non-invasive home monitoring of biovital parameters in RTT. Moreover, for the first time, HRmax% and the HR/LF ratio were identified as potential objective markers of fatigue, illness severity, and disease progression.
PubMed: 38952469
DOI: 10.3389/fneur.2024.1388506 -
Veterinary Medicine and Science Jul 2024Acute flaccid paralysis (AFP) is a complex clinical syndrome with various aetiologies. If untreated, AFP may lead to death due to failure of respiratory muscles. Tick...
BACKGROUND
Acute flaccid paralysis (AFP) is a complex clinical syndrome with various aetiologies. If untreated, AFP may lead to death due to failure of respiratory muscles. Tick paralysis, which is a noninfectious neurologic syndrome of AFP, occurs following tick attachment, engorgement, and injection of tick saliva toxins. There is no specific diagnostic test for tick paralysis, and mortality increases as definitive diagnosis is delayed. Although metabolomic investigation of tick saliva was conducted, there is a lack of research on metabolomic evaluation of hosts affected by tick paralysis.
OBJECTIVES
Thus, the aim of this study is to investigate metabolomic changes in serum samples of dogs with tick paralysis due to Rhipicephalus sanguineus using NMR-based metabolomics and to identify potential diagnostic/prognostic markers.
MATERIALS AND METHODS
Forty dogs infested with R. sanguineus, with clinical findings compatible with AFP and with a confirmed tick paralysis diagnosis ex juvantibus, constituted the Paralysis Group. Ten healthy dogs, which were admitted either for vaccination and/or check-up purposes, constituted the Control Group. After the confirmation tick paralysis, medical history, vaccination and nutritional status, body surface area and estimated tick numbers of all the dogs were noted. Physical examination included body temperature, heart and respiratory rate, capillary refill time evaluation and Modified Glasgow Coma Scale calculation. Serum samples were extracted from venous blood samples of all the dogs and were prepared for NMR analysis, and NMR-based metabolomics identification and quantification were performed.
RESULTS
NMR-based serum metabolomics of the present study revealed distinct up/down-regulated expressions, presenting a promising avenue. Moreover, it was observed that energy metabolism and especially liver functions were impaired in dogs with tick paralysis, and not only the respiratory system but also the kidneys were affected.
CONCLUSION
It was concluded that the present approach may help to better understand the pathological mechanisms developing in cases of AFP due to tick paralysis.
Topics: Animals; Dogs; Tick Paralysis; Dog Diseases; Magnetic Resonance Spectroscopy; Metabolomics; Female; Male; Rhipicephalus sanguineus; Metabolome; Paralysis
PubMed: 38952268
DOI: 10.1002/vms3.1528