Mapping interictal discharges using intracranial EEG-fMRI to predict postsurgical outcomes.

Various subjective and objective methods have been proposed to identify which interictal epileptiform discharge (IED)-related EEG-fMRI results are more likely to delineate seizure generating tissue in patients with drug-resistant focal epilepsy for the purposes of surgical planning. In this intracranial EEG-fMRI study, we evaluated the utility of these methods to localize clinically relevant regions pre-operatively and compared the extent of resection of these areas to post-operative outcome. Seventy patients admitted for intracranial video-EEG monitoring were recruited for a simultaneous intracranial EEG-fMRI study. For all analyses of blood oxygen level-dependent responses associated with IEDs, an experienced epileptologist identified the most Clinically Relevant brain activation cluster using available clinical information. The Maximum cluster (the cluster with the highest z-score) was also identified for all analyses and assigned to one of three confidence levels (low, medium, or high) based on the difference of the peak z-scores between the Maximum and Second Maximum cluster (the cluster with the second highest peak z-value). The distance was measured and compared between the peak voxel of the aforementioned clusters and the electrode contacts where the interictal discharge and seizure onset were recorded. In patients who subsequently underwent epilepsy surgery, the spatial concordance between the aforementioned clusters and the area of resection was determined and compared to post-operative outcome. We evaluated 106 different IEDs in 70 patients. Both subjective (identification of the Clinically Relevant cluster) and objective (Maximum cluster much more significant than the second maximum cluster) methods of culling non-localizing EEG-fMRI activation maps increased the spatial concordance between these clusters and the corresponding IED or seizure onset zone contacts. However, only the objective methods of identifying medium and high confidence maps resulted in a significant association between resection of the peak voxel of the Maximum cluster and post-operative outcome. Resection of this area was associated with good post-operative outcomes but was not sufficient for seizure freedom. On the other hand, we found that failure to resect the medium and high confidence Maximum clusters was associated with a poor post-surgical outcome (negative predictive value = 1.0, sensitivity = 1.0). Objective methods to identify higher confidence EEG-fMRI results are needed to localize areas necessary for good post-operative outcomes. However, resection of the peak voxel within higher confidence Maximum clusters is not sufficient for good outcomes. Conversely, failure to resect the peak voxel in these clusters is associated with a poor post-surgical outcome.

Experimental Inoculation of Pigs with Monkeypox Virus Results in Productive Infection and Transmission to Sentinels.

Monkeypox virus (MPXV) is a re-emerging zoonotic poxvirus responsible for producing skin lesions in humans. Endemic in sub-Saharan Africa, the 2022 outbreak with a clade IIb strain has resulted in ongoing sustained transmission of the virus worldwide. MPXV has a relatively wide host range, with infections reported in rodent and non-human primate species. However, the susceptibility of many domestic livestock species remains unknown. Here, we report on a susceptibility/transmission study in domestic pigs that were experimentally inoculated with a 2022 MPXV clade IIb isolate or served as sentinel contact control animals. Several principal-infected and sentinel contact control pigs developed minor lesions near the lips and nose starting at day 12 through 18 days post-challenge (DPC). No virus was isolated or viral DNA was detected from the lesions; however, MPXV antigen was detected by IHC in tissue from a pustule of a principal infected pig. Viral DNA and infectious virus were detected in nasal and oral swabs up to 14 DPC, with peak titers observed at 7 DPC. Viral DNA was also detected in nasal tissues or skin collected from two principal-infected animals at 7 DPC post-mortem. Furthermore, all principal-infected and sentinel control animals enrolled in the study seroconverted. In conclusion, we provide the first evidence that domestic pigs are susceptible to experimental MPXV infection and can transmit the virus to contact animals.

A randomized phase II trial to examine modified vaccinia Ankara-5T4 vaccine in patients with relapsed asymptomatic ovarian cancer (TRIOC).

BACKGROUND: Immunotherapy directed at 5T4 tumor antigen may delay the need for further chemotherapy. An attenuated modified vaccinia Ankara virus containing the gene encoding for 5T4 (MVA-5T4) was studied in asymptomatic relapsed ovarian cancer. OBJECTIVE: To assess the effectiveness and safety of MVA-5T4 as treatment for asymptomatic relapsed ovarian cancer. METHODS: TRIOC was a phase II randomized (1:1), placebo-controlled, double-blind multicenter study. The primary aim was to assess the effectiveness and safety of MVA-5T4 as a treatment for asymptomatic patients with relapsed ovarian cancer. Eligible patients had International Federation of Gynecology and Obstetrics (FIGO) stage IC1-III or IVA epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, Eastern Cooperative Oncology Group (ECOG) 0-1, with relapse defined by a rise in CA-125 to twice the upper limit of normal or low-volume disease on CT scan. The primary endpoint was disease progression (including deaths from ovarian cancer) at 25 weeks. Following a brief suspension, the trial restarted as a single-arm study. The revised single-arm design required 45 evaluable patients treated with MVA-5T4 to detect a 25-week progression rate of 50%, assuming an expected 70% rate without MVA-5T4; 85% power with one-sided 5% significance. RESULTS: A total of 94 eligible patients were recruited, median age was 65 years (range 42-82), median follow-up 34 months (range 2-46). Overall, 59 patients received MVA-5T4 and 35 patients received placebo. The median number of MVA-5T4 injections received was 7 (range 0-9), compared with a median of 6 (range 1-12) for patients receiving placebo. Median progression-free survival was the same in both arms (3.0 months). The 25-week progression rate was similar in both arms: 80.0% for patients treated with MVA-5T4 and 85.7% for those receiving placebo (risk difference -5.7%, 95% CI -21.4% to 10.0%). Median time to clinical intervention was improved with MVA-5T4: 7.6 months (range 6.7-9.5) vs 5.6 (range 4.9-7.6), CONCLUSION: MVA-5T4 vaccination in patients with asymptomatic relapse was well-tolerated but did not improve the progression rate at 25 weeks. The majority of patients who received MVA-5T4 had clinical intervention later than those assigned to placebo. TRIAL REGISTRATION NUMBER: NCT01556841.

Transcatheter-Based Interventions for Tetralogy of Fallot Across All Age Groups.

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. Palliative procedures, either surgical or transcatheter, aim to improve oxygen saturation, affording definitive procedures at a later stage. Transcatheter interventions have been used before and after surgical palliative or definitive repair in children and adults. This review aims to provide an overview of the different catheter-based interventions for TOF across all age groups, with an emphasis on palliative interventions, such as patent arterial duct stenting, right ventricular outflow tract stenting, or balloon pulmonary valvuloplasty in infants and children and transcatheter pulmonary valve replacement in adults with repaired TOF, including the available options for a large, dilated native right ventricular outflow tract.

Endovascular removal of a large free-floating thrombus of the descending thoracic aorta using the AngioVac system.

Free-floating aortic mural thrombus in the minimally diseased or nonaneurysmal aorta is a rare, clinically significant source of peripheral embolism. We describe a 41-year-old woman with a history of left brachial thromboembolectomy who presented atypical chest pain. Computed tomography angiography and transesophageal echocardiography revealed a 14.0 cm × 1.4 cm mobile mass in the proximal descending thoracic aorta. The thrombus was removed through a minimally invasive catheter-based approach using the AngioVac system.

Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi.

The globally distributed marine alga Emiliania huxleyi has cooling effect on the Earth's climate. The population density of E. huxleyi is restricted by Nucleocytoviricota viruses, including E. huxleyi virus 201 (EhV-201). Despite the impact of E. huxleyi viruses on the climate, there is limited information about their structure and replication. Here, we show that the dsDNA genome inside the EhV-201 virion is protected by an inner membrane, capsid, and outer membrane. EhV-201 virions infect E. huxleyi by using fivefold vertices to bind to and fuse the virus' inner membrane with the cell plasma membrane. Progeny virions assemble in the cytoplasm at the surface of endoplasmic reticulum-derived membrane segments. Genome packaging initiates synchronously with the capsid assembly and completes through an aperture in the forming capsid. The genome-filled capsids acquire an outer membrane by budding into intracellular vesicles. EhV-201 infection induces a loss of surface protective layers from E. huxleyi cells, which enables the continuous release of virions by exocytosis.

Finding structure during incremental speech comprehension.

A core aspect of human speech comprehension is the ability to incrementally integrate consecutive words into a structured and coherent interpretation, aligning with the speaker's intended meaning. This rapid process is subject to multidimensional probabilistic constraints, including both linguistic knowledge and non-linguistic information within specific contexts, and it is their interpretative coherence that drives successful comprehension. To study the neural substrates of this process, we extract word-by-word measures of sentential structure from BERT, a deep language model, which effectively approximates the coherent outcomes of the dynamic interplay among various types of constraints. Using representational similarity analysis, we tested BERT parse depths and relevant corpus-based measures against the spatiotemporally resolved brain activity recorded by electro-/magnetoencephalography when participants were listening to the same sentences. Our results provide a detailed picture of the neurobiological processes involved in the incremental construction of structured interpretations. These findings show when and where coherent interpretations emerge through the evaluation and integration of multifaceted constraints in the brain, which engages bilateral brain regions extending beyond the classical fronto-temporal language system. Furthermore, this study provides empirical evidence supporting the use of artificial neural networks as computational models for revealing the neural dynamics underpinning complex cognitive processes in the brain.

WSV2023 - The second meeting of the world society for virology: One health - One world - One virology.

The Second International Conference of the World Society for Virology (WSV), hosted by Riga Stradins University, was held in Riga, Latvia, on June 15-17th, 2023. It prominently highlighted the recent advancements in different disciplines of virology. The conference had fourteen keynote speakers covering diverse topics, including emerging virus pseudotypes, Zika virus vaccine development, herpesvirus capsid mobility, parvovirus invasion strategies, influenza in animals and birds, West Nile virus and Marburg virus ecology, as well as the latest update in animal vaccines. Discussions further explored SARS-CoV-2 RNA replicons as vaccine candidates, SARS-CoV-2 in humans and animals, and the significance of plant viruses in the 'One Health' paradigm. The presence of the presidents from three virology societies, namely the American, Indian, and Korean Societies for Virology, highlighted the event's significance. Additionally, past president of the American Society for Virology (ASV), formally declared the partnership between ASV and WSV during the conference.

Editorial Commentary: Anterior Cruciate Ligament Repair or Reconstruction With Internal Bracing, for Properly Indicated Patients, Is Safe, Biocompatible, and Biomimetic.

Anterior cruciate ligament (ACL) reconstruction with internal bracing (IB)-and ACL repair with IB when indicated-reduces graft or repair failure. IB is safe and protects ligament reconstructions and repairs. The IB construct should not be misunderstood as a synthetic ligament. To be effective, suture tape must be independently secured with the knee in full extension, reflecting the terminal length of the ACL. Regardless of graft type, the graft must be cyclically tensioned independent of the IB to allow for creep, and when properly performed, this significantly increases the ultimate tensile strength of the construct and reduces graft elongation, without stress shielding. Thus, the generic term "suture augmentation" may be misleading because the successful results reported apply to the IB technique. In our experience, the failure rate after ACL reconstruction with IB is 1% at the 5-year follow-up period. Notably, these results were achieved without an additional lateral extra-articular procedure.

Rift Valley Fever.

Rift Valley fever (RVF) is a zoonotic viral disease that affects domestic and wild ruminants such as cattle, sheep, goats, camels, and buffaloes. Rift valley fever virus (RVFV), the causative agent of RVF, can also infect humans. RVFV is an arthropod-borne virus (arbovirus) that is primarily spread through the bites of infected mosquitoes or exposure to infected blood. RVFV was first isolated and characterized in the Rift Valley of Kenya in 1931 and is endemic throughout sub-Saharan Africa, including Comoros and Madagascar, the Arabian Peninsula (Saudi Arabia and Yemen), and Mayotte.

Evaluating Temperature Effects on Bluetongue Virus Serotype 10 and 17 Coinfection in Culicoides sonorensis.

Bluetongue virus (BTV) is a segmented, double-stranded RNA virus transmitted by Culicoides midges that infects ruminants. As global temperatures increase and geographical ranges of midges expand, there is increased potential for BTV outbreaks from incursions of novel serotypes into endemic regions. However, an understanding of the effect of temperature on reassortment is lacking. The objectives of this study were to compare how temperature affected Culicoides survival, virogenesis, and reassortment in Culicoides sonorensis coinfected with two BTV serotypes. Midges were fed blood meals containing BTV-10, BTV-17, or BTV serotype 10 and 17 and maintained at 20 °C, 25 °C, or 30 °C. Midge survival was assessed, and pools of midges were collected every other day to evaluate virogenesis of BTV via qRT-PCR. Additional pools of coinfected midges were collected for BTV plaque isolation. The genotypes of plaques were determined using next-generation sequencing. Warmer temperatures impacted traits related to vector competence in offsetting ways: BTV replicated faster in midges at warmer temperatures, but midges did not survive as long. Overall, plaques with BTV-17 genotype dominated, but BTV-10 was detected in some plaques, suggesting parental strain fitness may play a role in reassortment outcomes. Temperature adds an important dimension to host-pathogen interactions with implications for transmission and evolution.

Clinical relevance and therapeutic predictive ability of hypoxia biomarkers in head and neck cancer tumour models.

Tumour hypoxia promotes poor patient outcomes, with particularly strong evidence for head and neck squamous cell carcinoma (HNSCC). To effectively target hypoxia, therapies require selection biomarkers and preclinical models that can accurately model tumour hypoxia. We established 20 patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) models of HNSCC that we characterised for their fidelity to represent clinical HNSCC in gene expression, hypoxia status and proliferation and that were evaluated for their sensitivity to hypoxia-activated prodrugs (HAPs). PDX models showed greater fidelity in gene expression to clinical HNSCC than cell lines, as did CDX models relative to their paired cell lines. PDX models were significantly more hypoxic than CDX models, as assessed by hypoxia gene signatures and pimonidazole immunohistochemistry, and showed similar hypoxia gene expression to clinical HNSCC tumours. Hypoxia or proliferation status alone could not determine HAP sensitivity across our 20 HNSCC and two non-HNSCC tumour models by either tumour growth inhibition or killing of hypoxia cells in an ex vivo clonogenic assay. In summary, our tumour models provide clinically relevant HNSCC models that are suitable for evaluating hypoxia-targeting therapies; however, additional biomarkers to hypoxia are required to accurately predict drug sensitivity.

Rift Valley Fever virus M and L genome segment detection: a comparison of field-deployable reverse transcription insulated isothermal PCR (RT-iiPCR) and laboratory-based multiplex reverse transcription real-time PCR.

Rift Valley Fever phlebovirus (RVFV) is a mosquito-borne zoonotic pathogen that causes major agricultural and public health problems in Africa and the Arabian Peninsula. It is considered a potential agro-bioterrorism agent for which limited countermeasures are available. To address diagnostic needs, here we describe a rapid and sensitive molecular method immediately employable at sites of suspected outbreaks in animals that commonly precede outbreaks in humans. The strategy involves the concurrent detection of two of the three RVFV genome segments (large and medium) using reverse transcription insulated isothermal PCR (RT-iiPCR) performed on a portable, touch screen nucleic acid analyzer, POCKIT. The analytical sensitivity for both the RT-iiPCR and a laboratory-based L and M multiplex reverse transcription real-time PCR assay was estimated at approximately 0.1-3 copies/reaction using synthetic RNA or viral RNA. The diagnostic sensitivity and specificity of detection of RVFV on the POCKIT, determined using sera from sheep and cattle (n = 181) experimentally infected with two strains of RVFV (SA01 and Ken06), were 93.8% and 100% (kappa = 0.93), respectively. Testing of ruminant field sera (n = 193) in two locations in Africa demonstrated 100% diagnostic sensitivity and specificity. We conclude that the POCKIT dual-gene RVFV detection strategy can provide reliable, sensitive, and specific point-of-need viral RNA detection. Moreover, the field detection of RVFV in vectors or susceptible animal species can aid in the surveillance and epidemiological studies to better understand and control RVFV outbreaks. IMPORTANCE: The content of this manuscript is of interest to the diverse readership of the Journal of Clinical Microbiology, including research scientists, diagnosticians, healthcare professionals, and policymakers. Rift Valley Fever virus (RVFV) is a zoonotic mosquito-borne pathogen that causes major agricultural and public health problems. Current and most sensitive diagnostic approaches that are molecular-based are performed in highly specialized molecular diagnostic laboratories. To address diagnostic needs, we developed a novel, rapid, and sensitive molecular method using a portable PCR machine, POCKIT, capable of immediate deployment at sites of suspected outbreaks. Here, we demonstrate that field-deployable RVFV detection can provide reliable, sensitive, and specific point-of-need viral RNA detection that could be used for diagnostic investigations and epidemiological studies, and can be performed in the field.

Efficacy of noncarbapenem therapy for the treatment of ceftriaxone-resistant Enterobacterales outside the urinary tract.

Objective: To determine the safety of noncarbapenem versus carbapenem antibiotics for treatment of adults with documented infection caused by ceftriaxone-resistant infections outside the urinary tract. Design: Retrospective cohort of adult patients with a documented infection caused by an extended-spectrum ß-lactamase (ESBL)-producing organism isolated between January 2018 and October 2021. Setting: An academic tertiary-care center. Patients: Adult patients with a documented infection caused by an ESBL-producing organism outside the urinary tract. Methods: The primary outcome was a composite of treatment failure defined as 30-day mortality, 30-day readmission, microbiological recurrence, and/or clinical worsening requiring antibiotic change. Secondary outcomes included differentiation of primary composite components and postantibiotic Clostridioides difficile infection (CDI). Results: This study included 130 patients. The primary source of infections were bloodstream (67.7%) and caused by Escherichia coli (81.5%). Overall, 101 patients received carbapenem therapy and 29 received noncarbapenem therapy (NCT). NCT was comprised of mainly fluoroquinolones (18 of 29) followed by cefepime (7 of 29). Patients receiving NCT had shorter hospital stays (median, 7 days vs 9 days) and were more often discharged on antibiotics (79.3% vs 50.5%). We did not detect a significant difference in the primary composite outcome of treatment failure for carbapenem (23.8%) versus noncarbapenem treatment (24.2%; P = .967). Secondary outcomes included a numerically higher 30-day mortality rate in the noncarbapenem group compared to the carbapenem group: 4 (13.8%) of 29 versus 4 (3.9%) of 101. We did not detect a difference in rates of CDI. Conclusion: Noncarbapenem therapy may play a role for certain patients with infections caused by ESBL-producing organisms.

Racial effects on masimo pulse oximetry: impact of low perfusion index.

PURPOSE:  Evaluate the SpO2-SaO2 difference between Black and White volunteer subjects having a low perfusion index (Pi) compared to those having a normal Pi. METHODS:  The Pi data were abstracted from electronic files collected on 7183 paired SpO2-SaO2 samples (3201 Black and 3982 White) from a recently reported desaturation study of 75 subjects (39 Black and 36 White) where SaO2 values were sequentially decreased from 100 to 70%. The Pi values from that dataset were divided into two groups (Pi ≤ 1 or Pi > 1) for analysis. A Pi value ≤ 1 was considered "low perfusion" and a Pi value > 1 was considered "normal perfusion". Statistical calculations included values of bias (mean difference of SpO2-SaO2), precision (standard deviation of the difference), and accuracy (root-mean-square error [ARMS]). During conditions of low perfusion (Pi ≤ 1, range [0.1 to 1]), overall bias and precision were + 0.48% ± 1.59%, while bias and precision were + 0.19 ± 1.53%, and + 0.91 ± 1.57%, for Black and White subjects, respectively. RESULTS:  During normal perfusion (Pi > 1, range [1 to 12]), overall bias and precision were + 0.18% ± 1.34%, while bias and precision were -0.26 ± 1.37%, and - 0.12 ± 1.31%, for Black and White subjects, respectively. ARMS was 1.37% in all subjects with normal perfusion and 1.64% in all subjects with low perfusion. CONCLUSION:  Masimo SET® pulse oximeters with RD SET® sensors are accurate for individuals of both Black and White races when Pi is normal, as well as during conditions when Pi is low. The ARMS for all conditions studied is well within FDA standards. This study was conducted in healthy volunteers during well-controlled laboratory desaturations, and results could vary under certain challenging clinical conditions.

Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections.

PURPOSE: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants. METHODS: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells. RESULTS: Biallelic variants in CRELD1 were found in 18 participants from 14 families. Affected individuals displayed an array of phenotypes involving developmental delay, early-onset epilepsy, and hypotonia, with about half demonstrating cardiac arrhythmias and some experiencing recurrent infections. Most harbored a frameshift in trans with a missense allele, with 1 recurrent variant, p.(Cys192Tyr), identified in 10 families. X tropicalis tadpoles with creld1 knockdown displayed developmental defects along with increased susceptibility to induced seizures compared with controls. Additionally, human CRELD1 harboring missense variants from affected individuals had reduced protein function, indicated by a diminished ability to induce craniofacial defects when overexpressed in X tropicalis. Finally, baseline analyses of peripheral blood mononuclear cells showed similar proportions of immune cell subtypes in patients compared with healthy donors. CONCLUSION: This patient cohort, combined with experimental data, provide evidence of a multisystem clinical syndrome mediated by recessive variants in CRELD1.

Cryptic bacterial pathogens of diatoms peak during senescence of a winter diatom bloom.

Diatoms are globally abundant microalgae that form extensive blooms in aquatic ecosystems. Certain bacteria behave antagonistically towards diatoms, killing or inhibiting their growth. Despite their crucial implications to diatom blooms and population health, knowledge of diatom antagonists in the environment is fundamentally lacking. We report systematic characterisation of the diversity and seasonal dynamics of bacterial antagonists of diatoms via plaque assay sampling in the Western English Channel (WEC), where diatoms frequently bloom. Unexpectedly, peaks in detection did not occur during characteristic spring diatom blooms, but coincided with a winter bloom of Coscinodiscus, suggesting that these bacteria likely influence distinct diatom host populations. We isolated multiple bacterial antagonists, spanning 4 classes and 10 bacterial orders. Notably, a diatom attaching Roseobacter Ponticoccus alexandrii was isolated multiple times, indicative of a persistent environmental presence. Moreover, many isolates had no prior reports of antagonistic activity towards diatoms. We verified diatom growth inhibitory effects of eight isolates. In all cases tested, these effects were activated by pre-exposure to diatom organic matter. Discovery of widespread 'cryptic' antagonistic activity indicates that bacterial pathogenicity towards diatoms is more prevalent than previously recognised. Finally, examination of the global biogeography of WEC antagonists revealed co-occurrence patterns with diatom host populations in marine waters globally.

Experimental co-infection of calves with SARS-CoV-2 Delta and Omicron variants of concern.

Since emerging in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly crossed the species barrier with natural infections reported in various domestic and wild animal species. The emergence and global spread of SARS-CoV-2 variants of concern (VOCs) has expanded the range of susceptible host species. Previous experimental infection studies in cattle using Wuhan-like SARS-CoV-2 isolates suggested that cattle were not likely amplifying hosts for SARS-CoV-2. However, SARS-CoV-2 sero- and RNA-positive cattle have since been identified in Europe, India, and Africa. Here, we investigated the susceptibility and transmission of the Delta and Omicron SARS-CoV-2 VOCs in cattle. Eight Holstein calves were co-infected orally and intranasally with a mixed inoculum of SARS-CoV-2 VOCs Delta and Omicron BA.2. Twenty-four hours post-challenge, two sentinel calves were introduced to evaluate virus transmission. The co-infection resulted in a high proportion of calves shedding SARS-CoV-2 RNA at 1- and 2-days post-challenge (DPC). Extensive tissue distribution of SARS-CoV-2 RNA was observed at 3 and 7 DPC and infectious virus was recovered from two calves at 3 DPC. Next-generation sequencing revealed that only the SARS-CoV-2 Delta variant was detected in clinical samples and tissues. Similar to previous experimental infection studies in cattle, we observed only limited seroconversion and no clear evidence of transmission to sentinel calves. Together, our findings suggest that cattle are more permissive to infection with SARS-CoV-2 Delta than Omicron BA.2 and Wuhan-like isolates but, in the absence of horizontal transmission, are not likely to be reservoir hosts for currently circulating SARS-CoV-2 variants.

Descriptive evaluation of patients receiving one-time intravenous vancomycin doses at a large academic medical center emergency department.

BACKGROUND: Intravenous (IV) vancomycin is commonly used to treat a variety of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The practice of administering a single dose of IV vancomycin prior to emergency department (ED) discharge may be clinically ineffective and foster antimicrobial resistance. Furthermore, this practice introduces an unnecessary infection risk along with preventable adverse effects while potentially increasing ED length of stay (LOS). There is a paucity of literature identifying patient characteristics and objective findings in this patient population, which may foster future antimicrobial stewardship initiatives in the ED. METHODS: This was a single-center, retrospective, descriptive analysis of adult patients seen in the ED between January 2020 and January 2023 who received a single dose of IV vancomycin and were subsequently discharged from the ED without hospital admission. Information was collected on patient demographics and select comorbidities, vancomycin indication and dosing, ED LOS, initial vitals and labs, concomitant antibiotics administered, culture results, 30-day return ED visits and admissions, and antibiotics prescribed at ED discharge. RESULTS: A total of 295 patients met inclusion criteria. A total of 32.1% of patients met SIRS criteria. The most commonly selected order indication for IV vancomycin was "skin and skin structure infection" (41%). A total of 86.1% of patients received concomitant antibiotics in the ED and only 54.6% of patients were prescribed oral antibiotics at ED discharge. A total of 80% of patients had at least one culture obtained during the ED visit. In those who had at least one culture obtained, 78.4% of patients had negative cultures and 4.2% of patients had MRSA positive cultures, with MRSA skin cultures being the most common (3.1%). Return ED visits and admissions within 30 days were not statistically significantly different between patients who did and did not receive oral antibiotics at ED discharge. CONCLUSIONS: Despite a lack of clinical efficacy reported in prior literature and the potential risks, administration of a one-time dose of IV vancomycin prior to ED discharge is commonly encountered in clinical practice. There are opportunities for enhanced antimicrobial stewardship related to IV vancomycin use in the ED. Areas of future focus include the utilization of oral antimicrobials when clinically appropriate, particularly for skin and soft tissue infections, and clarification of antibiotic allergies.

Preliminary Study on the Efficacy of a Recombinant, Subunit SARS-CoV-2 Animal Vaccine against Virulent SARS-CoV-2 Challenge in Cats.

The objective of this work was to evaluate the safety and efficacy of a recombinant, subunit SARS-CoV-2 animal vaccine in cats against virulent SARS-CoV-2 challenge. Two groups of cats were immunized with two doses of either a recombinant SARS-CoV-2 spike protein vaccine or a placebo, administered three weeks apart. Seven weeks after the second vaccination, both groups of cats were challenged with SARS-CoV-2 via the intranasal and oral routes simultaneously. Animals were monitored for 14 days post-infection for clinical signs and viral shedding before being humanely euthanized and evaluated for macroscopic and microscopic lesions. The recombinant SARS-CoV-2 spike protein subunit vaccine induced strong serologic responses post-vaccination and significantly increased neutralizing antibody responses post-challenge. A significant difference in nasal and oral viral shedding, with significantly reduced virus load (detected using RT-qPCR) was observed in vaccinates compared to mock-vaccinated controls. Duration of nasal, oral, and rectal viral shedding was also significantly reduced in vaccinates compared to controls. No differences in histopathological lesion scores were noted between the two groups. Our findings support the safety and efficacy of the recombinant spike protein-based SARS-CoV-2 vaccine which induced high levels of neutralizing antibodies and reduced nasal, oral, and rectal viral shedding, indicating that this vaccine will be efficacious as a COVID-19 vaccine for domestic cats.