Early Infection Research Articles

Incidence and prevention of early postoperative infection in orthopedic surgery

Incidence and prevention of early postoperative infection in orthopedic surgery

The Pathognomonic ultrasonographic findings in fetus with COVID-19 infection

Aim: The main goal is to identify the pathognomonic sonographic signs for foetal SARS-CoV-2 infection and to determine whether or not transplacental SARS-CoV-2 transmission is possible. Patients and Methods: In total, 105 pregnant women with positive SARS-CoV-2 PCR swabs during the first trimester with mild or moderate infection without hospitalisation and/or oxygen support were included in this prospective comparative study, which was carried out at the ultrasound and foetal medicine unit of Ain Shams University Maternity Hospital from January 2021 to June 2023. The SARS-CoV-2 positive group was compared to the control group with inclusion and exclusion criteria. Results: In the COVID-19 group, pathognomonic ultrasonographic results were considerably more common. The COVID-19 group had a considerably higher frequency of placental calcifications and oligohydramnios. In the COVID-19 cohort, patients with positive pathognomonic ultrasonographic results had considerably higher BMIs. In the COVID-19 cohort, gestational age at infection, and BMI ≥30.0 kg/m2 were significant independent risk factors for the development of pathognomonic ultrasonographic abnormalities. Those in the control group who had positive pathognomonic ultrasonographic results were older and had higher rates of hypertension. Significant independent risk variables for the incidence of pathognomonic ultrasonographic findings in the control group included age ≥34.0 years and hypertension. Conclusion: There is no evidence of a teratogenic effect linked to maternal SARS-CoV-2 infection during the first few months of pregnancy. However, early pregnancy infection with COVID-19 is linked to pathognomonic ultrasonography findings of placental calcifications and oligohydramnios.

Early Periprosthetic Joint Infections in Total Hip and Knee Arthroplasty: Microorganisms, Mortality, and Implant Survival Using a Combined Dataset From the Dutch Arthroplasty Register and the Dutch National Nosocomial Surveillance Network

BackgroundPeriprosthetic joint infections (PJIs) can lead to higher re-revision rates and even higher mortality rates that may be associated with the responsible microorganism. We evaluated microorganisms that cause early PJIs in primary total hip and knee arthroplasty (THA and TKA) and examined mortality as well as PJI re-revision rates after these PJIs, using a combined dataset from the Dutch Arthroplasty Register and the Dutch National Nosocomial Surveillance Network (PREZIES). Secondly, the most common microorganisms that cause PJIs were described according to patient and implant survival. MethodsWe included all PREZIES-confirmed PJIs (n = 1,648) from the combined dataset in which primary THAs and TKAs (2012 to 2018) from the Dutch Arthroplasty Register and PREZIES were case-level matched. Kaplan-Meier survival analyses were performed to determine mortality and PJI re-revision rates following PJI revision. ResultsThe most prevalent microorganism in THAs and TKAs was Staphylococcus aureus (THA 34%; TKA 39%), followed by Coagulase-negative staphylococci (THA 20%; TKA 19%), with Staphylococcus epidermidis (THA 12%; TKA 11%) as the most common subtype, and Enterococcus species (THA 8.6%; TKA 5.9%). The 5-year mortality was 15% (95% confidence interval [CI]: 13 to 18) and 18% (CI: 14 to 21) for THA and TKA patients, respectively. The 5-year PJI re-revision rate was 28% (CI: 24 to 34) for THAs and 30% (CI: 24 to 38) for TKAs. In deceased THA patients who had a PJI, Enterococcus species (14%) were more often registered as microorganisms responsible for the PJI than S. epidermidis (8.5%). ConclusionsOver half of the early PJIs in THAs and TKAs in the Netherlands were caused by Staphylococcus aureus and Coagulase-negative staphylococci including Staphylococcus epidermidis. Both 5-year mortality and PJI re-revision rates following PJI were relatively high.

Quantitative phosphoproteomics reveals molecular pathway network in wheat resistance to stripe rust

Protein phosphorylation plays an important role in immune signaling transduction in plant resistance to pathogens. Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), severely devastates wheat production. Nonetheless, the molecular mechanism of wheat resistance to stripe rust remains limited. In this study, quantitative phosphoproteomics was employed to investigate the protein phosphorylation changes in wheat challenged by Pst. A total of 1537 and 2470 differentially accumulated phosphoproteins (DAPs) were identified from four early infection stage (6, 12, 18 and 24 h post-inoculation) in incompatible and compatible wheat-Pst interactions respectively. KEGG analysis revealed that Oxidative Phosphorylation, Phosphatidylinositol Signaling, and MAPK signaling processes are distinctively enriched in incompatible interaction, while Biosynthesis of secondary metabolites and RNA degradation process were significantly enriched in compatible interactions. In particular, abundant changes in phosphorylation levels of chloroplast proteins were identified, suggesting the regulatory role of photosynthesis in wheat-Pst interaction, which is further emphasized by protein-protein interaction (PPI) network analysis. Motif-x analysis identified [xxxxSPxxxx] motif, likely phosphorylation sites for defensive response-related kinases, and a new [xxxxSSxxxx] motif significantly enriched in incompatible interaction. The results shed light on the early phosphorylation events contributing to wheat resistance against Pst. Moreover, our study demonstrated that the phosphorylation levels of Nucleoside diphosphate kinase TaNAPK1 are upregulated at 12 hpi with CYR23 and at 24 hpi with CYR31. Transient silencing of TaNAPK1 was able to attenuate wheat resistance to CYR23 and CYR31. Our study provides new insights into the mechanisms underlying Pst-wheat interactions and may provide database to find potential targets for the development of new resistant varieties.

Neuropilin-1 is a novel host factor modulating the entry of hepatitis B virus

Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV. However, hepatocytes expressing NTCP exhibit varying susceptibilities to HBV infection. This study aimed to investigate whether other host factors modulate the process of HBV infection. Liver biopsy samples obtained from children with hepatitis B were used for single-cell sequencing and susceptibility analysis. Primary human hepatocytes, HepG2-NTCP cells, and human liver chimeric mice were used to analyze the effect of candidate host factors on HBV infection. Single-cell sequencing and susceptibility analysis revealed a positive correlation between neuropilin-1 (NRP1) expression and HBV infection. In the HBV-infected cell model, NRP1 overexpression before HBV inoculation significantly enhanced viral attachment and internalization, and promoted viral infection in the presence of NTCP. Mechanistic studies indicated that NRP1 formed a complex with LHBs (large hepatitis B surface proteins) and NTCP. The NRP1 b domain mediated its interaction with conserved arginine residues at positions 88 and 92 in the preS1 domain of LHBs. This NRP1-preS1 interaction subsequently promoted the binding of preS1 to NTCP, facilitating viral infection. Moreover, disruption of the NRP1-preS1 interaction by the NRP1 antagonist EG00229 significantly attenuated the binding affinity between NTCP and preS1, thereby inhibiting HBV infection both invitro and invivo. Our findings indicate that NRP1 is a novel host factor for HBV infection, which interacts with preS1 and NTCP to modulate HBV entry into hepatocytes. HBV infection is a global public health problem, but the understanding of the early infection process of HBV remains limited. Through single-cell sequencing, we identified a novel host factor, NRP1, which modulates HBV entry by interacting with HBV preS1 and NTCP. Moreover, antagonists targeting NRP1 can inhibit HBV infection both invitro and invivo. This study could further advance our comprehension of the early infection process of HBV.

Clinical characteristics and outcomes associated with culture-negative status in limb osteomyelitis patients

AimsThis study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.MethodsA total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts.ResultsOf these patients, 264 (25.2%) had negative cultures. Patients with a culture-negative compared with a culture-positive status were more likely to have the following characteristics: younger age (≤ 40 years) (113/264 (42.8%) vs 257/783 (32.8%); p = 0.004), a haematogenous aetiology (75/264 (28.4%) vs 150/783 (19.2%); p = 0.002), Cierny-Mader host A (79/264 (29.9%) vs 142/783 (18.1%); p < 0.001), antibiotic use before sampling (34/264 (12.9%) vs 41/783 (5.2%); p＜0.001), fewer taken samples (n＜3) (48/264 (18.2%) vs 60/783 (7.7%); p＜0.001), and less frequent presentation with a sinus (156/264 (59.1%) vs 665/783 (84.9%); p < 0.001). After initial treatments of first-debridement and antimicrobial, infection eradication was inferior in culture-positive osteomyelitis patients, with a 2.24-fold increase (odds ratio 2.24 (95% confidence interval 1.42 to 3.52)) in the redebridement rate following multivariate analysis. No statistically significant differences were found in long-term recurrence and complications within the two-year follow-up.ConclusionWe identified several factors being associated with the culture-negative result in osteomyelitis patients. In addition, the data also indicate that culture negativity is a positive prognostic factor in early infection eradication. These results constitute the basis of optimizing clinical management and patient consultations.Cite this article: Bone Joint J 2024;106-B(7):720–727.

New insights into swine dysentery: faecal shedding, macro and microscopic lesions and biomarkers in early and acute stages of Brachyspira hyodysenteriae infection

BackgroundSwine dysentery (SD) is a severe mucohaemorrhagic colitis in pigs caused classically by Brachyspira hyodysenteriae. Although several aspects of B. hyodysenteriae infection dynamic are already described, further research in the early stage of this infection is required. In this study, 7-week-old pigs were orally challenged with B. hyodysenteriae to obtain information about faecal shedding, macro and microscopic intestinal lesions and serum acute phase proteins in pigs at the onset of B. hyodysenteriae shedding (early infection group, n = 8), in pigs with mucohaemorrhagic diarrhoea (acute infection group, n = 8) and in non-infected controls (n = 16).ResultsFirst B. hyodysenteriae detection by q-PCR and first loose stools with blood and mucus occurred both at 8 days post-inoculation. The lapse between a positive q-PCR and observation of mucohaemorrhagic diarrhoea ranged from 0 to 3 days, except in a single pig in which this period lasted 5 days. Macroscopic lesions were observed in the large intestine from both infected groups although more frequent and severe in acute infection group. Microscopic observation of the apex mucosa revealed that in early infection only higher ulceration values were observed compared to healthy controls. In contrast, the acute infection group exhibited higher ulceration, neutrophils infiltration and increased mucosal thickness compared to the other two groups. Among the serum biomarkers tested, only haptoglobin, C-reactive protein, and creatine kinase showed a significant increase in pigs in the acute infection period compared to controls, whereas haptoglobin was the only factor with a significant increase at the early infection compared to non-infected animals.ConclusionsThis study provides new insights about SD and remarks the complex and limited options to perform an early detection of infected animals beyond PCR diagnosis.

NKp30 and NKG2D contribute to natural killer recognition of HIV-infected cells.

Natural killer (NK) cells respond rapidly in early HIV-1 infection. HIV-1 prevention and control strategies harnessing NK cells could be enabled by mechanistic understanding of how NK cells recognize HIV-infected T cells. Here, we profiled the phenotype of human primary NK cells responsive to autologous HIV-1-infected CD4 + T cells in vitro. We characterized the patterns of NK cell ligand expression on CD4 + T cells at baseline and after infection with a panel of transmitted/founder HIV-1 strains to identify key receptor-ligand pairings. CRISPR editing of CD4 + T cells to knockout the NKp30 ligand B7-H6, or the NKG2D ligands MICB or ULBP2 reduced NK cell responses to HIV-infected cells in some donors. In contrast, overexpression of NKp30 or NKG2D in NK cells enhanced their targeting of HIV-infected cells. Collectively, we identified receptor-ligand pairs including NKp30:B7-H6 and NKG2D:MICB/ULBP2 that contribute to NK cell recognition of HIV-infected cells.

Helminth induced monocytosis conveys protection from respiratory syncytial virus infection in mice.

Respiratory syncytial virus (RSV) infection in infants is a major cause of viral bronchiolitis and hospitalisation. We have previously shown in a murine model that ongoing infection with the gut helminth Heligmosomoides polygyrus protects against RSV infection through type I interferon (IFN-I) dependent reduction of viral load. Yet, the cellular basis for this protection has remained elusive. Given that recruitment of mononuclear phagocytes to the lung is critical for early RSV infection control, we assessed their role in this coinfection model. Mice were infected by oral gavage with H. polygyrus. Myeloid immune cell populations were assessed by flow cytometry in lung, blood and bone marrow throughout infection and after secondary infection with RSV. Monocyte numbers were depleted by anti-CCR2 antibody or increased by intravenous transfer of enriched monocytes. H. polygyrus infection induces bone marrow monopoiesis, increasing circulatory monocytes and lung mononuclear phagocytes in a IFN-I signalling dependent manner. This expansion causes enhanced lung mononuclear phagocyte counts early in RSV infection that may contribute to the reduction of RSV load. Depletion or supplementation of circulatory monocytes prior to RSV infection confirms that these are both necessary and sufficient for helminth induced antiviral protection. H. polygyrus infection induces systemic monocytosis contributing to elevated mononuclear phagocyte numbers in the lung. These cells are central to an anti-viral effect that reduces the peak viral load in RSV infection. Treatments to promote or modulate these cells may provide novel paths to control RSV infection in high risk individuals.

Performance of a rapid recency assay for detection of early HIV infection

The Asanté HIV-1 Rapid Recency assay's ‘verification’ line detected HIV infection a median of 18 days later than a nucleic acid detection assay and performed similarly to 19 other existing rapid HIV antibody tests. Pending regulatory approval, the assay could be an option with other rapid tests in national HIV-1 testing algorithms, which would allow collection of HIV recency data as part of a national screening program without requiring additional testing.

Thermography Research in Diabetic Foot: Insights From a Scopus-Based Bibliometric Study.

Diabetic foot problems are among the most debilitating complications of diabetes mellitus. These problems incur significant economic costs and reduce quality of life. The integration of thermography technology in the screening and management of diabetic foot problems has been proven to be successful in recent years. By detecting changes in temperature, thermography helps identify early infections and assists in patient monitoring. These early successes have inspired more research and publications in this field. To date, a comprehensive bibliometric analysis of thermography-related research on diabetic foot using the Scopus database has not been conducted. This bibliometric analysis aims to fill this gap by reviewing the Scopus database from its inception until 2023 to examine the literature on thermography-related research on diabetic foot. A total of 342 articles met the selection criteria and were included in this analysis. The number of articles in this field remained low until the 2010s, when there was a sudden surge of interest that prompted numerous publications. Authors from the USA contributed the highest number of articles and had the greatest scholarly impact in this field. Despite the major contribution from the USA, there were numerous collaborations between various countries, underscoring the importance of international collaboration in advancing research and exchanging knowledge.

Enterococcus-related vascular graft infection: A case series

ObjectivesWe aimed to assess the frequency, management, and burden of enterococcal-related vascular graft infection. Patients and methodsFrom 2008 to 2021, data regarding all episodes of vascular graft infections initially managed or secondarily referred to our referral center were prospectively collected. We described the history and management of the infection, depending on the type of prosthesis used. ResultsThe frequency of enterococcal-related vascular graft infections was 29/249 (12 %). Most of them were early infections (22/29, 76 %). Infections were polymicrobial (26/29, 90 %), mostly associated with Enterobacterales. Among patients with positive blood cultures, 7/8 (88 %) involved enterococci. Patients with enterococcal-related vascular graft infections were mainly (22/29, 76 %) treated with an association of antibiotics. Mortality and relapse occurred in 28 % and 7 % respectively of the cases. ConclusionsEnterococcal-related vascular graft infections occurred in patients with comorbidities, during the early period following surgery and were more frequent in cases of intra-cavitary prosthesis. Their potential virulence needs to be considered, especially in polymicrobial infections.

Pharmacokinetic/pharmacodynamic issues for optimizing treatment with beta-lactams of Gram-negative infections in critically ill orthotopic liver transplant recipients: a comprehensive review

Orthotopic liver transplant (OLT) represents the standard of care for managing patients affected by end-stage and life-threatening liver diseases. Although a significant improvement in surgical techniques, immunosuppressant regimens, and prompt identification of early post-transplant complications resulted in better clinical outcome and survival in OLT recipients, the occurrence of early bacterial infections still represents a remarkable cause of morbidity and mortality. In this scenario, beta-lactams are the most frequent antimicrobials used in critical OLT recipients. The aim of this narrative review was to provide a comprehensive overview of the pathophysiological issues potentially affecting the pharmacokinetics of beta-lactams and to identify potential strategies for maximizing the likelihood of attaining adequate pharmacokinetic/pharmacodynamic (PK/PD) targets of beta-lactams in critically ill OLT recipients. A literature search was carried out on PubMed-MEDLINE database (until 31st March 2024) in order to retrieve clinical trials, real-world observational evidence, and/or case series/reports evaluating the PK/PD of traditional and novel beta-lactams in settings potentially involving critically ill OLT recipients. Retrieved evidence were categorized according to the concepts of the so-called “antimicrobial therapy puzzle”, specifically assessing a) beta-lactam PK/PD features, with specific regard to aggressive PK/PD target attainment; b) site of infection, with specific regard to beta-lactam penetration in the lung, ascitic fluid, and bile; and c) pathophysiological alterations, focusing mainly on those specifically associated with OLT. Overall, several research gaps still exist in assessing the PK behavior of beta-lactams in critical OLT recipients. The impact of specific OLT-associated pathophysiological alterations on the attainment of optimal PK/PD targets may represent an important field in which further studies are warranted. Assessing the relationship between aggressive beta-lactam PK/PD target attainment and clinical outcome in critical OLT recipients will represent a major challenge in the next future.

Augmented cement shelf acetabuloplasty to improve hip stability in elderly patients with recurrent hemiarthroplasty dislocations

Background The treatment of dislocated hip hemiarthroplasty in low-demand elderly patients is controversial due to poor results with closed reduction, and significant complications with exchange arthroplasty. This case series demonstrates the use of a novel, simple surgical technique for hip hemiarthroplasty containment without resorting to exchange arthroplasty. Methods Eleven patients where screw-augmented cement shelf acetabuloplasty procedures were performed were retrospectively identified. All surgeries were performed by a single attending surgeon, at a level-one trauma center, from 2015 to 2022. Previous dislocations, interventions, co-morbidities, mobility level, and posterior wall deficiency were recorded from the patient's charts. The following outcome measures were recorded: operative time, blood loss, perioperative complications, early and late infections, shelf loosening, subsequent dislocations, and the need for additional procedures. Results The median duration between hip hemiarthroplasty and shelf procedure was 56 days. The mean duration of the surgical procedure was only 63 min, and the mean blood loss was only 250 mL. There was only one instance of loosening of the cement shelf. Two patients had surgical site infections leading to sepsis and death. In two patients, the femoral head was exchanged to improve stability. All patients were allowed immediate weight bearing after the procedure. Conclusions Shelf acetabuloplasty is a simple, inexpensive, and safe procedure to salvage recurrent hip hemiarthroplasty dislocation in low-demand patients. Shorter surgical duration, relatively lower blood loss, and immediate weight bearing render this an attractive procedure for this fragile population.

Design of Monkeypox Disease Diagnosis Model Using Classical Machine Learning Algorithm

Monkeypox is a zoonotic viral disease that the World Health Organization (WHO) reported as an epidemic in 2022. In most nations, the rate of these illness infections started to rise over time. Monkeypox can be caught directly from an infected person or via animal contact. In this study, an artificial intelligence-based diagnostic model for early monkeypox infection detection is developed. The proposed method is based on building a model based on KNN, SVC, Random Forest, Naive Bayes and Gradient Boosting for the classification problem. A voting method was also used to determine the final diagnosis of the proposed model. The system was trained and evaluated using a dataset that represented the clinical signs of monkeypox infection. The dataset comprises one hundred twenty infected patients and 120 typical cases out of 240 probable cases. The suggested model attained 75% accuracy.

Association Between Early Sexual Debut and New HIV Infections Among Adolescents and Young Adults in 11 African Countries

We investigated the association between early sexual debut and HIV infection among adolescents and young adults. Analyzing data from nationally representative Population-Based HIV Impact Assessment (PHIA) surveys in 11 African countries, the research employed a multivariate logistic regression model to assess the relationship between the early sexual debut and new HIV infections in the age group of 10–24 years. The results revealed a significant and robust association, indicating that young individuals who experienced early sexual debut were approximately 2.65 times more likely to contract HIV than those who did not, even after accounting for other variables. These findings align with prior research suggesting that early initiation of sexual activity may increase vulnerability to HIV infection due to factors such as biological susceptibility and risky behaviors like low condom use and multiple sexual partners. The implications of these findings for HIV prevention strategies are substantial, suggesting that interventions aimed at delaying sexual debut could be an effective component in reducing HIV risk for this population. Targeted sex education programs that address the risks of early sexual debut may play a pivotal role in these prevention efforts. By employing a comprehensive approach, there is a possibility to advance efforts towards ending AIDS by 2030.

Characterization of a lipid-based jumbo phage compartment as a hub for early phage infection

Viral genomes are most vulnerable to cellular defenses at the start of the infection. A family of jumbo phages related to phage ΦKZ, which infects Pseudomonas aeruginosa, assembles a protein-based phage nucleus to protect replicating phage DNA, but how it is protected prior to phage nucleus assembly is unclear. We find that host proteins related to membrane and lipid biology interact with injected phage protein, clustering in an early phage infection (EPI) vesicle. The injected virion RNA polymerase (vRNAP) executes early gene expression until phage genome separation from the vRNAP and the EPI vesicle, moving into the nascent proteinaceous phage nucleus. Enzymes involved in DNA replication and CRISPR/restriction immune nucleases are excluded by the EPI vesicle. We propose that the EPI vesicle is rapidly constructed with injected phage proteins, phage DNA, host lipids, and host membrane proteins to enable genome protection, early transcription, localized translation, and to ensure faithful genome transfer to the proteinaceous nucleus.

Identification of a circulating long non-coding RNA signature panel in plasma as a novel biomarker for the detection of acute/early-stage HIV-1 infection

BackgroundIndividuals with acute / early HIV-1 infection are often unaware that they are infected with HIV-1 and may be involved in high-risk behavior leading to transmission of HIV-1. Identifying individuals with acute / early HIV-1 infection is critical to prevent further HIV-1 transmission, as diagnosis can lead to several effective HIV-1 prevention strategies. Identification of disease-stage specific non-viral host biomarkers would be useful as surrogate markers to accurately identify new HIV-1 infections. The goal of this study was to identify a panel of host derived plasma long non-coding RNAs (lncRNAs) that could serve as prognostic and predictive biomarkers to detect early/acute HIV-1 infection.MethodsA total of 84 lncRNAs were analyzed in sixteen plasma samples from HIV-1 infected individuals and four healthy controls using the lncRNA PCR-array. Twenty-one lncRNAs were selected and validated in 80 plasma samples from HIV-1 infected individuals [HIV-1 infected patients in the eclipse stage (n = 20), acute stage (n = 20), post-seroconversion p31 negative stage (n = 20), and post-seroconversion p31 positive stage (n = 20) of infection] and 20 healthy controls. The validation study results were used to develop a plasma lncRNA panel that was evaluated in the panel test phase to detect early/acute HIV-1 infection in 52 independent samples.ResultsWe identified a lncRNA panel (Pmodel−I) containing eight lncRNAs (DISC2, H19, IPW, KRASP1, NEAT1, PRINS, WT1-AS and ZFAS1) that could distinguish HIV-1 infection from healthy controls with high AUC 0·990 (95% CI 0.972-1.000), sensitivity (98.75%), and specificity (95%). We also found that Pmodel−II and Pmodel−III demonstrates 100% sensitivity and specificity (AUC 1·00; 95%CI:1·00–1·00) and could distinguish eclipse stage and acute stage of HIV-1 infection from healthy controls respectively. Antiretroviral treatment (ART) cumulatively restored the levels of lncRNAs to healthy controls levels.ConclusionlncRNA expression changes significantly in response to HIV-1 infection. Our findings also highlight the potential of using circulating lncRNAs to detect both the eclipse and acute stages of HIV-1 infection, which may help to shorten the window period and facilitate early detection and treatment initiation. Initiating ART treatment at this stage would significantly reduce HIV-1 transmission. The differentially expressed lncRNAs identified in this study could serve as potential prognostic and diagnostic biomarkers of HIV-1 infection, as well as new therapeutic targets.

WGS of intrauterine E. coli from cows with early postpartum uterine infection reveals a non-uterine specific genotype and virulence factors.

Escherichia coli has been attributed to playing a major role in a cascade of events that affect the prevalence and severity of uterine disease in cattle. The objectives of this project were to (i) define the association between the prevalence of specific antimicrobial resistance and virulence factor genes in E. coli with the clinical status related to uterine infection, (ii) identify the genetic relationship between E. coli isolates from cows with diarrhea, with mastitis, and with and without metritis, and (iii) determine the association between the phenotypic and genotypic antimicrobial resistance identified on the E. coli isolated from postpartum cattle. Bacterial isolates (n = 148) were obtained from a larger cross-sectional study. Cows were categorized into one of three clinical groups before enrollment: metritis, cows with purulent discharge, and control cows. For genomic comparison, public genomes (n = 130) from cows with diarrhea, mastitis, and metritis were included in a genome-wide association study, to evaluate differences between the drug classes or the virulence factor category among clinical groups. A distinct E. coli genotype associated with metritis could not be identified. Instead, a high genetic diversity among the isolates from uterine sources was present. A virulence factor previously associated with metritis (fimH) using PCR was not associated with metritis. There was moderate accuracy for whole-genome sequencing to predict phenotypic resistance, which varied depending on the antimicrobial tested. Findings from this study contradict the traditional pathotype classification and the unique intrauterine E. coli genotype associated with metritis in dairy cows.IMPORTANCEMetritis is a common infectious disease in dairy cattle and the second most common reason for treating a cow with antimicrobials. The pathophysiology of the disease is complex and is not completely understood. Specific endometrial pathogenic Escherichia coli have been reported to be adapted to the endometrium and sometimes lead to uterine disease. Unfortunately, the specific genomic details of the endometrial-adapted isolates have not been investigated using enough genomes to represent the genomic diversity of this organism to identify specific virulence genes that are consistently associated with disease development and severity. Results from this study provide key microbial ecological advances by elucidating and challenging accepted concepts for the role of Intrauterine E. coli in metritis in dairy cattle, especially contradicting the existence of a unique intrauterine E. coli genotype associated with metritis in dairy cows, which was not found in our study.

Antiviral Activities of Mastoparan-L-Derived Peptides against Human Alphaherpesvirus 1.

Human alphaherpesvirus 1 (HSV-1) is a significantly widespread viral pathogen causing recurrent infections that are currently incurable despite available treatment protocols. Studies have highlighted the potential of antimicrobial peptides sourced from Vespula lewisii venom, particularly those belonging to the mastoparan family, as effective against HSV-1. This study aimed to demonstrate the antiviral properties of mastoparans, including mastoparan-L [I5, R8], mastoparan-MO, and [I5, R8] mastoparan, against HSV-1. Initially, Vero cell viability was assessed in the presence of these peptides, followed by the determination of antiviral activity, mechanism of action, and dose-response curves through plaque assays. Structural analyses via circular dichroism and nuclear magnetic resonance were conducted, along with evaluating membrane fluidity changes induced by [I5, R8] mastoparan using fluorescence-labeled lipid vesicles. Cytotoxic assays revealed high cell viability (>80%) at concentrations of 200 µg/mL for mastoparan-L and mastoparan-MO and 50 µg/mL for [I5, R8] mastoparan. Mastoparan-MO and [I5, R8] mastoparan exhibited over 80% HSV-1 inhibition, with up to 99% viral replication inhibition, particularly in the early infection stages. Structural analysis indicated an α-helical structure for [I5, R8] mastoparan, suggesting effective viral particle disruption before cell attachment. Mastoparans present promising prospects for HSV-1 infection control, although further investigation into their mechanisms is warranted.